bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential regulation of lineage commitment in human and mouse primed pluripotent stem cells by NuRD
Authors: Ragheb Ramy , Gharbi Sarah , Cramard Julie , Ogundele Oluwaseun , Kloet Susan , Burgold Thomas , Vermeulen Michiel , Reynolds Nicola , Hendrich Brian
Published: February 2020

Differentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The NuRD complex is a highly conserved chromatin remodeller which fine-tunes gene expression in embryonic stem cells. While the function of NuRD in mouse pluripotent cells has been well defined, no study yet has defined NuRD function in human pluripotent cells. We investigated the structure and function of NuRD in human induced pluripotent stem cells (hiPSCs). Using immunoprecipitation followed by mass-spectrometry in hiPSCs and in naive or primed mouse pluripotent stem cells, we find that NuRD structure and biochemical interactors are generally conserved. Using RNA sequencing, we find that, whereas in mouse primed stem cells and in mouse naïve ES cells, NuRD is required for an appropriate level of transcriptional response to differentiation signals, hiPSCs require NuRD to initiate these responses. This difference indicates that mouse and human cells interpret and respond to induction of differentiation differently.

Graphical Abstract

NuRD acts like a conductor in an orchestra.

A.In the presence of NuRD (pink blob figure, centre) differentiation occurs in an ordered fashion in both mouse (left) and human (right) ES cells. Gene expression changes in both cell types are tightly controlled with down-regulation of pluripotency genes and up-regulation of lineage appropriate genes. This is akin to a group of musicians producing musical notes in the right order and at the right amplitude to create a coherent piece of music.B.Loss of “the conductor” NuRD results in increased transcriptional noise in both systems, indicated here as a low-level blanket of sound in both systems. Consequences of MBD3/NuRD loss differs between human and mouse ES cells. In mouse ES cells, differentiation cues lead to some down-regulation of pluripotency genes and incomplete progression along a lineage appropriate pathway. This is like musicians who know that they should be making music but who lose their way without a conductor’s influence. In human iPS cells the background level of noise without NuRD results in a lack of order to gene expression changes in response to differentiation. The noise from these “musicians” would be truly awful.
An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq
Authors: Cresser-Brown Joel , Rizkallah Pierre , Jin Yi , Roth Christian , Miller David J. , Allemann Rudolf K.
Published: February 2020

Calpain is a Ca2+-activated, heterodimeric cysteine protease consisting of a large catalytic subunit and a small regulatory subunit. Dysregulation of this enzyme is involved in a range of pathological conditions such as cancer, Alzheimer's disease and rheumatoid arthritis, and thus calpain I is a drug target with potential therapeutic applications. Difficulty in the production of this enzyme has hindered structural and functional investigations in the past, although heterodimeric calpain I can be generated by Escherichia coli expression in low yield. Here, an unexpected structure discovered during crystallization trials of heterodimeric calpain I (CAPN1C115S + CAPNS1ΔGR) is reported. A novel co-crystal structure of the PEF(S) domain from the dissociated regulatory small subunit of calpain I and the RNA-binding chaperone Hfq, which was likely to be overproduced as a stress response to the recombinant expression conditions, was obtained, providing unexpected insight in the chaperone function of Hfq.
Towards a solution of the inverse X-ray diffraction tomography challenge: theory and iterative algorithm for recovering the 3D displacement field function of Coulomb-type point defects in a crystal
Authors: Chukhovskii Felix N. , Konarev Petr V. , Volkov Vladimir V.
Published: February 2020

The theoretical framework and a joint quasi-Newton–Levenberg–Marquardt–simulated annealing (qNLMSA) algorithm are established to treat an inverse X-ray diffraction tomography (XRDT) problem for recovering the 3D displacement field functionfCtpd(r−r0) =h · u(r−r0) due to a Coulomb-type point defect (Ctpd) located at a pointr0within a crystal [his the diffraction vector andu(r−r0) is the displacement vector]. The joint qNLMSA algorithm operates in a special sequence to optimize the XRDT target function {\cal F}\{ {\cal P} \} in a χ2sense in order to recover the functionfCtpd(r−r0) [{\cal P} is the parameter vector that characterizes the 3D functionfCtpd(r−r0) in the algorithm search]. A theoretical framework based on the analytical solution of the Takagi–Taupin equations in the semi-kinematical approach is elaborated. In the case of true 2D imaging patterns (2D-IPs) with low counting statistics (noise-free), the joint qNLMSA algorithm enforces the target function {\cal F} \{ {\cal P} \} to tend towards the global minimum even if the vector {\cal P} in the search is initially chosen rather a long way from the true one.
Causes of delay to public infrastructure projects according to engineers representing different contract parties
Authors: Ahmad Hesham S. , Ayoush Maha D. , Al-Alwan Majed S.
Published: February 2020

Purpose

The purpose of this paper is to investigate the main causes of delay in public construction projects. This is motivated by feedback from public construction experts concerning substantive delays during the last decade. The study thus seeks to help decision makers in Jordan and elsewhere identify problems and develop mitigating strategies.

Design/methodology/approach

Causes of delay were identified from previous related studies and then augmented after consultation with experts. This resulted in 56 delay factors classified into eight groups. The sampling frame for the study was defined in terms of public construction projects (mostly related to roads) owned by the Ministry of Public Works and Housing in Jordan. A survey was conducted with engineers working as representatives of the owner, contractors or consultants to elicit and evaluate the importance of the 56 delay factors.

Findings

Overall, 113 completed questionnaire responses were returned and analyzed to rank the causes of delay using the relative importance index method. Owners and consultants showed more interest in factors related to themselves, while contractors showed highest interest in an external factor related to the owner of services. Four recommendations are put forward for decision makers to mitigate against delays.

Originality/value

This research investigates a relatively large number of delay factors compared to other studies and these are categorized into groups to facilitate thematic understanding. Further, compared to previous related research, this research fills a gap by exploring the opinions of different contract parties.
Drivers of efficiency and their influence on airline performances in South Africa: a bootstrapped meta-frontier approach
Authors: Mhlanga Oswald
Published: February 2020

Purpose

This paper aims to identify drivers of efficiency and their influence on airline performances in South Africa. Unfortunately, the methods currently used to measure airline efficiency fail to address the heterogeneity problem, which blurs inefficiency.

Design/methodology/approach

To remedy the heterogeneity problem, this paper adopts the meta-frontier framework to identify drivers of efficiency. The interesting feature of the model is that it ensures that heterogeneous airlines are compared based on one homogeneous technology. The model is tested using a panel data sample of nine South African airlines, which operated from 2015 to 2018.

Findings

The paper demonstrates that structural drivers, namely, “aircraft size”, and “airline ownership” and one executional driver, namely, “the cost structure” significantly influence (p < 0.05) airline efficiency thereby corroborating evidence from some prior studies.

Research limitations/implications

First, because of the small size of the industry, fewer airlines and a lack of detailed data, the study could not consider other important factors such as optimal routing and network structure. Second, a more rigorous analysis over a period of time would yield better understanding about the growth of the industry in South Africa and recognise the variation in the influence of drivers of efficiency on airline performances over time.

Practical implications

The results have potential policy implications. First, as the market in South Africa is too small to operate with a smaller aircraft probably, for airlines that operate with smaller aircraft to operate efficiently they should first identify niche markets where they can have a route monopoly. Second, while all state-owned airlines are perfect statehood symbols that define and represent countries, most state carriers in South Africa are highly inefficient. The researcher recommends policymakers to privatise state airlines or seek equity partners. Many nationalised airlines have turned losses to profits in the run-up to privatisation. British Airways, once a large burden on the British taxpayer, is now one of the world’s most efficient airlines. After the privatisation of Air France and Iberia, all two turned from loss-making concerns into profitable airlines. It, therefore, makes no sense for the South African government to expect state carriers to pursue a commercial mandate with such political interference. The very notion of efficiency itself is at risk.

Originality/value

This paper is a first attempt to identify drivers of operational efficiency using a bootstrapped meta-frontier approach in the airline industry in South Africa. By applying the meta-frontier approach the paper ensures that all heterogeneous airlines are assessed based on their distance from a common and identical frontier.
Can mass media be an obstacle to rationing decisions? A case report from Portugal
Authors: Pinho Micaela , Dias Costa Eva
Published: February 2020

Purpose

Continuous introduction of advanced health technologies coupled with limited resources force governments to adopt rationing measures in all types of health systems. The mass media can influence the application of these measures by rising people and patients' expectations and demands for new forms of healing. This article intends to find evidence of this influence by reporting two recent cases which occurred in Portugal involving two innovative drugs, one for the treatment of hepatitis C and another for type I spinal muscular atrophy. The new drugs were not publicly funded despite promising excellent overall health outcomes because of their high cost and exaggerated burden on national health system (NHS).

Design/methodology/approach

A qualitative research was used to collect information conveyed by the conventional media and social networks.

Findings

After a strong dissemination through conventional and social media of the nonapproved treatments, the drugs swiftly garnered support among the public and triggered remarkable and relentless advocacy efforts. The findings of this paper suggest that society opinions and, by extension, the decision of policy-makers are very susceptible to the influence of the mass media.

Practical implications

New ways of sharing information are changing health research and public health.

Social implications

These stories raise complex tensions and important questions about resource-allocation decisions involving scientific research or innovative medicine. Societal preferences seem very vulnerable to information conveyed by the mass media.

Originality/value

This study is the first attempt to awaken attention to the influence that Portuguese mass media may exercise on future healthcare rationing decisions.
Challenges of 21st-century health governance
Authors: MacVane Phipps Fiona
Published: February 2020

Purpose

The purpose of this review is to provide an overview of the articles included within one issue of International Journal of Health Governance (IJHG) together with some commentary and reference to other published works.

Design/methodology/approach

The design is a literature review based on the articles in the current issue of IJHG. Other literature studies are referred to for expansion or clarification of the discussion.

Findings

Finding ways to provide efficient, equitable and compassionate care continues to occupy the minds of health managers and health professionals.

Originality/value

The originality value lies in the fact that IJHG is the only journal in the Emerald suite of health care–related publications that includes a regular review of this type.
Altruism as a pathway to unethical action
Authors: Babula Michael , Tookey Max , Muschert Glenn , Neal Mark
Published: February 2020

Purpose

The purpose of this paper is to answer the question, “Can particular types of altruism influence people to make unethical decisions?” The purpose of seeking to answer this question is to better understand those cases in personal, public and commercial life whereby a decision-maker is influenced by what is widely perceived to be a positive thing – altruism – to make unethical choices.

Design/methodology/approach

An experiment was designed to test the influence of different categories of altruism on decision-making about whether to find another guilty for a regulatory transgression. This involved the establishment and running of a student panel at a UK university, which was given the task of determining the guilt or otherwise of two students accused of plagiarism – one from a poor background; one from a rich background. Through a survey of both the decision-makers and their judgments, and by analyzing the data using t-tests and Mann–Whitney tests, the associations between different categories of altruism and the decisions made could be ascertained.

Findings

A total of 70.7% of the participants voted “not-guilty” for the poor student, whereas 68.3% voted “guilty” for the wealthy student. This indicated that self-interested, namely, egoistic altruism complemented by social and self-esteem needs gratification was significantly associated with violating foundational ethical principles.

Originality/value

This is the first study to be done that attempts to evaluate the relationships between different categories of altruism and ethical decision-making. The findings here challenge aggregating all forms of empathy together when exploring the antecedents of unethical behavior.
Why would anyone come to Corfu to have a Heineken?
Authors: Melewar T.C. , Skinner Heather
Published: February 2020

Purpose

This paper aims to examine brand-naming decisions, along with other management decisions that affect tourist experiences, such as visitor tours and souvenir appropriation, in the context of a microbrewery located on a Greek island that remains heavily dependent upon tourism.

Design/methodology/approach

Data were gathered from in-depth interviews with the microbrewery’s owner and senior management team to offer rich insights into the issues under investigation.

Findings

Findings stress the importance of the meanings that can be conveyed through brand names, including those that indicate authenticity of the brand’s origin, filling previously identified gaps in the literature on country of origin (COO) with regard to fast-consuming goods and low-involvement products such as beer, and exploring the issue of experiential consumption of beer as part of the tourists’ vacation experience.

Research limitations/implications

Data were gathered from only a single company, and although highlighting important managerial decisions regarding brand naming, further research could be widened to other companies and other industries, and could explore these issues from the tourists own perspective rather than solely from a managerial perspective.

Practical implications

Results may offer insights for local producers, particularly small and medium-sized enterprises, whose markets serve both domestic and tourist consumers.

Originality/value

This research furthers knowledge into gaps on a range of issues arising in the literature that have hitherto not been previously linked, specifically: product COO/brand origin, cultural consumption of beverages and sense of place, issues of authenticity, souvenirs and experiential consumption.
Service brand rehab: diagnosing trust repair mechanisms
Authors: Bolat Elvira , Robson Julie , Sit Kokho Jason , Birch-Chapman Shannon , Ashraf Samreen , Memery Juliet , Jackson Caroline
Published: February 2020

Purpose

This paper aims to understand consumers’ response to the trust repair mechanisms adopted by corporate brands in a service sector context following prominent trust damaging organizational transgressions.

Design/methodology/approach

Adopting a qualitative approach, six focus group discussions are used to investigate three high-profile consumer trust erosion cases within the service sector.

Findings

Consumer trust varies by context. Despite the severity of trust damage, corporate brands can recover trust towards their brands amongst consumers not directly affected by transgressions. Not all trust repair mechanisms are equally applicable to all service contexts, and re-branding could be used as a trust repair mechanism. Corporate brands in the service sector should focus on sense-making, relational approaches and transparency. Orchestration of trust repair mechanisms needs to be integrated within the trust rehabilitation processes.

Research limitations/implications

This study illustrates it is important to reconsider trust repair processes to accommodate context and integrate post-transgression consumer research.

Practical implications

Successful corporate brand rehabilitation of consumer trust requires examination of the trustworthiness dimensions consumers express before and after the transgression to select the most appropriate trust repair mechanisms. Findings suggest organizations also have preventative trust repair management programs.

Originality/value

This research is the first to empirically apply the conceptual framework of Bachmann et al. (2015) to explore consumer responses to the trust repair mechanisms adopted by corporate brands by context.
The selection model for horizontal alliances between hotels and airlines: an integrated application of NGT, fuzzy TOPSIS and MCGP methods
Authors: Fu Yan-Kai , Huang Weilun , Liao Chin-Nung
Published: February 2020

Purpose

The purpose of this paper is to evaluate the hotel selection problem of airlines for their hotel and airline alliance (HAA) to develop potential customers of airlines. This paper will propose a hybrid mathematics evaluation model to help airline to select an optimal hotel with both qualitative and quantitative criteria.

Design/methodology/approach

To solve the hotel selection problem of airlines for their HAA, this paper focuses on the implementation of the NGT, Fuzzy TOPSIS and MCGP models in the hotel selection process. Initially, the NGT was used to create HAA decision-making criteria based on the literature review and expert opinions, and it was found that scale and scope possibility, brand value, tourism attraction, operating cost and industrial conditions are the most important criteria. Later, the Fuzzy TOPSIS method was used to obtain the general normalized fuzzy preference and to compute the closeness coefficients of each alternative hotel with respect to each criterion. Third, five tangible constraints were incorporated into the Fuzzy TOPSIS-MCGP model to calculate the optimal hotel with LINGO software.

Findings

Airline managers can use the proposed model to form a clear view of how to choose the most suitable hotel to cooperate with to outperform their competitors. Having access to this information allows airline managers to take steps to perform better and improve the performance of the partnership, helping them to gain more confidence in their decision-making capabilities while reducing investment risks.

Originality/value

This is the first paper that has adopted Fuzzy TOPSIS-MCGP to select hotel for their HAA from the airline’s point of view. The major contributions of this study are as follows: an efficient and simple evaluation framework is proposed for handling vagueness and uncertainty in real-world hotel selection problems; the advancement of treating uncertainty in the MCDM process; the fuzzy TOPSIS-MCGP method is extended for such problems, taking into account tangible and intangible criteria; airline managers can now make decisions in choosing to select the best hotel for their HAA that meets the airline's business goals and passenger demands; hotel operators are flexible in selecting their airline partnership, thus creating greater profit for both parties.
Impact of user parameters in inversion velocity analysis
Authors: Zhou T. , Chauris H. , Audebert F.
Published: February 2020

Migration velocity analysis is a method devoted to the evaluation of both reflectivity and background velocity models, associated with the high and low wavenumber components of the model, respectively. Inversion velocity analysis is one of its improved versions, leading to more stable background velocity updates. Still, the impact of the user parameters should be understood for an optimal update of the background velocity. We show that a sign reversal of the background velocity gradient could occur when the selected surface offset range or the space lag range is too small. We derive the theoretical limits and check their consistency through simulations in a simple model with a single interface. These guidelines determine the necessary ranges of surface offsets and space lags for a proper update of the background velocity model. We discuss their applicability on the Marmousi model. Artefacts in the retrieved background velocity model are observed when the guidelines are not satisfied.
Soft and hard variables in determining pre‐service teachers' intentions and decisions to pursue a special education career
Authors: Zhang Dake , Whitford Denise K. , Hsu Hsien‐Yuan , Wang Yan
Published: February 2020

This study examined the roles of hard variables and soft variables in determining college teachers' intentions to pursue a special education career and education majors' actual decisions to major in special education. This study surveyed 243 college students taking special education courses at a state university, including 213 education majors. The survey questions included four blocks of variables, pertaining to demographics, training and work experience, soft variables (i.e., personal connections to people with disabilities, personal value and commitment and perceived social support) and hard variables (i.e., estimated salary, workload, professional development opportunities and job security). Results suggest that (1) after controlling for other variables, hard factors such as salary did not add significant contributions to college students' intention or education majors' actual action to pursue a special education career; (2) soft variables, such as value, commitment to special education and perceived social support, significantly predicted college students' intention to pursue a special education career, but did not significantly influence education majors' actual decision to choose a special education program, and (3) workloads significantly affect education majors' decisions making decisions of enrolling in a special education program. Implications are discussed about the importance of enhancing soft‐variable aspects of working conditions for special education recruitment and retention.
Home ownership as a labor market friction
Authors: Ringo Daniel R.
Published: February 2020

This paper estimates the effect of home ownership on individuals' unemployment. Because of higher moving costs, home owners will be less willing than renters to relocate for work and could therefore face longer unemployment spells. Estimation is complicated by the endogeneity of ownership, as owners will have different abilities, preferences, and job prospects than renters. I instrument for home ownership using a preference shifter from the worker's childhood environment. The results indicate that home ownership is a significant hindrance to mobility, and home owners suffer longer unemployment spells because of it.
Acknowledging Urbanization: A Survey of the Role of Cities in UN Frameworks
Authors: Kosovac Anna , Acuto Michele , Jones Terry Louise
Published: February 2020

Cities are playing an increasingly vital role in global sustainability. Yet there is still little systematic and international evidence on the recognition and formal role of cities in multilateral affairs. Where and how are cities acknowledged as part of global efforts? How do the United Nations frame this ‘urban’ contribution to major international processes and agendas? To offer some initial evidence‐based pointers to this set of problems, we present an analysis of explicit references to cities in major UN frameworks (n = 32) underpinning the current Agenda 2030 on sustainable development. We investigate how cities are cited to determine the role, key themes and contextual trends framing the engagement between United Nations and cities. Contra arguments for the uniqueness of the current ‘rise’ of mayors, our review demonstrates a weak rise in the recognition of cities over time in UN frameworks and shows historical continuity in this acknowledgement since the 1970s. Our review confirms that two prevailing themes determining this are those of ‘development’ and the ‘environment’ but other issues (like ‘infrastructure’ and ‘health’) are following closely behind. It also highlights acknowledgment of cities as ‘actors’ is on the rise since the 2000s and raises fundamental questions as to the status of cities internationally. We argue it becomes imperative to more systematically and strategically think of the role of cities in the UN system, but also flag that raises fundamental challenges for multilateral governance.
P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk
Authors: Zhang Yu , Jiang Min , Cui Ben‐Wen , Jin Cheng Hua , Wu Yan‐Ling , Shang Yue , Yang Hong‐Xu , Wu Mei , Liu Jian , Qiao Chun‐Ying , Zhan Zi‐Ying , Ye Huan , Zheng Guang‐Hao , Jin Quan , Lian Li‐Hua , Nan Ji‐Xing
Published: February 2020

Background and Purpose

Regulating macrophage–hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage–hepatocyte crosstalk during alcoholic hepatosteatosis.

Experimental Approach

A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP‐activated THP‐1 human macrophages with silenced or overexpressed P2X7 receptors. THP‐1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation. Western blots, RT‐PCR and immunohistochemical analysis were used, along with over‐expression and silencing of P2X7 receptors.

Key Results

Knockdown or overexpression of P2X7 receptors in THP‐1 macrophages affected release of mature IL‐1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB–AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1–AMPK–SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL‐1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase‐1 and NF‐κB, release of IL‐1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1–LKB1–AMPK–SREBP1 axis‐mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP‐activated THP‐1 macrophages pretreated with 2354glu.

Conclusion and Implications

Modulation of P2X7 receptors in macrophages regulated lipid accumulation in hepatocytes during alcoholic hepatosteatosis. 2354glu might be a promising candidate that targets P2X7 receptors in macrophages interacting with hepatocytes during alcoholic hepatosteatosis.
Mitochondrial behaviour, morphology, and animal performance
Authors: Heine Kyle B. , Hood Wendy R.
Published: February 2020

We have a limited understanding of the proximate mechanisms that are responsible for the development of variation in animal performance and life‐history strategies. Provided that components of an organism's successful life history – for example, mate competition, gestation, lactation, etc. – are energetically demanding, increased energy production within mitochondria is likely the foundation from which organisms are able to perform these tasks. Mitochondrial behaviour (positioning within the cell and communication between mitochondria) and morphology affect variation in energy production at the molecular, cellular, and organismal levels. Therefore, adaptations in mitochondrial behaviour and morphology that favour efficient energy production likely influence variation in animal performance. Previous work has linked greater proportions of inter‐mitochondrial junctions and density of the inner mitochondrial membrane, among other traits, with increased energetic demand. Future research should focus on how inter‐mitochondrial junctions and morphology of the inner mitochondrial membrane, in particular, influence animal performance in accordance with mitochondrial density, fission, and fusion.
Measuring shared decision making in oncology: Development and first testing of the iSHAREpatient and iSHAREphysician questionnaires
Authors: Bomhof‐Roordink Hanna , Gärtner Fania R. , van Duijn‐Bakker Nanny , van der Weijden Trudy , Stiggelbout Anne M. , Pieterse Arwen H.
Published: February 2020

Background

Existing measures to assess shared decision making (SDM) have often been developed based on an ill‐defined underlying construct, and many assess physician behaviours only or focus on a single patient‐physician encounter.

Objective

To (a) develop a patient and a physician questionnaire to measure SDM in oncology and (b) determine their content validity and comprehensibility.

Methods

A systematic review of SDM models and an oncology‐specific SDM model informed the domains of the SDM construct. We formulated items for each SDM domain. Cancer patients and physicians rated content validity in an online questionnaire. We assumed a formative measurement model and performed online field‐testing in cancer patients to inform further item reduction. We tested item comprehension in cognitive interviews with cancer patients and physicians.

Results

We identified 17 domains and formulated 132 items. Twelve cancer patients rated content validity at item level, and 11 physicians rated content validity at domain level. We field‐tested the items among 131 cancer patients and conducted cognitive interviews with eight patients and five physicians. These phases resulted in the 15‐item iSHAREpatient and 15‐item iSHAREphysician questionnaires, covering 13 domains.

Conclusions

We thoroughly developed the iSHARE questionnaires. They both assess patient and physician behaviours and cover the entire SDM process rather than a single consultation.
Patient and public involvement facilitators: Could they be the key to the NHS quality improvement agenda?
Authors: Todd Sarah , Coupland Christine , Randall Raymond
Published: February 2020

Objective

Research into patient and public involvement (PPI) has not examined in detail patient and public involvement facilitators’ (PPIFs) roles and activities. This study analysed PPIFs’ roles using qualitative data gathered from three different UK health‐care organizations.

Design

Thematic analysis was used to examine cross‐sectional data collected using a mixed‐methods approach from three organizations: a mental health trust, a community health social enterprise and an acute hospital trust. The data set comprised of 27 interviews and 48 observations.

Findings

Patient and public involvement facilitators roles included the leadership and management of PPI interventions, developing health‐care practices and influencing quality improvements (QI). They usually occupied middle‐management grades but their PPIF role involved working in isolation or in small teams. They reported facilitating the development and maintenance of relationships between patients and the public, and health‐care professionals and service managers. These roles sometimes required them to use conflict resolution skills and involved considerable emotional labour. Integrating information from PPI into service improvement processes was reported to be a challenge for these individuals.

Conclusions

Patient and public involvement facilitators capture and hold information that can be used in service improvement. However, they work with limited resources and support. Health‐care organizations need to offer more practical support to PPIFs in their efforts to improve care quality, particularly by making their role integral to developing QI strategies.
The IUPHAR Guide to Immunopharmacology: connecting immunology and pharmacology
Authors: Harding Simon D. , Faccenda Elena , Southan Christopher , Pawson Adam J. , Maffia Pasquale , Alexander Stephen P. H. , Davenport Anthony P. , Fabbro Doriano , Levi‐Schaffer Francesca , Spedding Michael , Davies Jamie A.
Published: February 2020

Given the critical role that the immune system plays in a multitude of diseases, having a clear understanding of the pharmacology of the immune system is crucial to new drug discovery and development. Here we describe the International Union of Basic and Clinical Pharmacology (IUPHAR) Guide to Immunopharmacology (GtoImmuPdb), which connects expert‐curated pharmacology with key immunological concepts and aims to put pharmacological data into the hands of immunologists. In the pursuit of new therapeutics, pharmacological databases are a vital resource to researchers through providing accurate information on the fundamental science underlying drug action. This extension to the existing IUPHAR/British Pharmacological Society Guide to Pharmacology supports research into the development of drugs targeted at modulating immune, inflammatory or infectious components of disease. To provide a deeper context for how the resource can support research we show data in GtoImmuPdb relating to a case study on the targeting of vascular inflammation.
Foxf2 and Smad6 co‐regulation of collagen 5A2 transcription is involved in the pathogenesis of intrauterine adhesion
Authors: Chen Guobin , Liu Limin , Sun Jing , Zeng Liying , Cai Huihua , He Yuanli
Published: February 2020

The replacement of normal endometrial epithelium by fibrotic tissue is the pathological feature of intrauterine adhesion (IUA), which is caused by trauma to the basal layer of the endometrium. COL5A2 is a molecular subtype of collagen V that regulates collagen production in fibrotic tissue. Here, we investigated the roles of Foxf2 and Smad6 in regulating the transcription of COL5A2 and their involvement in the pathogenesis of IUA. Small interference‐mediated Foxf2 (si‐Foxf2) silencing and pcDNA3.1‐mediated Smad6 (pcDNA3.1‐Smad6) up‐regulation were performed in a TGF‐β1‐induced human endometrial stromal cell line (HESC) fibrosis model. Assessment of collagen expression by Western blotting, immunofluorescence and qRT‐PCR showed that COL5A2, COL1A1 and FN were significantly down‐regulated in response to si‐Foxf2 and pcDNA3.1‐Smad6. Transfection of lentivirus vector‐Foxf2 (LV‐Foxf2) and pcDNA3.1‐Smad6 into HESCs and qRT‐PCR showed that Foxf2 promoted COL5A2 expression and Smad6 inhibited Foxf2‐induced COL5A2 expression. Co‐immunoprecipitation, chromatin immunoprecipitation and dual‐luciferase reporter assays to detect the interaction between Foxf2 and Smad6 and their role in COL5A2 transcription showed that Foxf2 interacted with Smad6 and bond the same promoter region of COL5A2. In a rat IUA model, injection of ADV2‐Foxf2‐1810 and ADV4‐Smad6 into the uterine wall showed that Foxf2 down‐regulation and Smad6 up‐regulation decreased fibrosis and the expression of COL5A2 and COL1A1, as detected by haematoxylin/eosin, Masson trichrome staining and immunohistochemistry. Taken together, these results suggested that Foxf2 interacted with Smad6 and co‐regulated COL5A2 transcription in the pathogenesis of IUA, whereas they played opposite roles in fibrosis.
Expression of Lefty predicts Merkel cell carcinoma‐specific death
Authors: Gambichler T. , Ardabili S. , Lang K. , Dreißigacker M. , Scheel C. , Brand‐Saberi B. , Skrygan M. , Stockfleth E. , Käfferlein H.U. , Brüning T. , Becker J.C.
Published: February 2020

Background

Lefty and Nodal are transforming growth factor β‐related proteins, which, beside their role in determination of laterality during embryogenesis, have also been linked with cancer progression.

Objectives

Prompted by the observed significant left‐sided laterality of Merkel cell carcinoma (MCC), we addressed whether Lefty and Nodal are expressed in MCC and correlated expression patterns with clinical parameters such as MCC laterality and patient outcome.

Methods

Expression of Lefty and Nodal in primary MCC was assessed in 29 patients by immunohistochemistry. The histology (H‐)score was calculated and correlated with clinical parameters.

Results

The median (range) H‐score of Lefty and Nodal was 17.6 (0–291) and 74.9 (0.7–272), respectively. There was a significant correlation between Lefty expression and Nodal expression (correlation coefficient of 0.60, P = 0.0006). There was no significant correlation between Lefty expression and Nodal expression with either tumour laterality, gender, age, Merkel cell polyomavirus status, disease stage, anatomical localization of primary tumours or disease relapse. On univariate analysis, low Lefty expression and Nodal expression were significantly associated with MCC‐specific death (P = 0.010 and P = 0.019, respectively). On univariate analysis, low Lefty expression was the only significant independent predictor for MCC‐specific death (P = 0.025) as indicated by an odds ratio of 14 (95% CI: 1.43–137.33).

Conclusions

Lefty and Nodal are frequently expressed in MCC, but not correlated with tumour laterality. Importantly, our data suggest that a low level of Lefty expression in primary MCC is a strong predictor of MCC‐specific death.
WHAT HAPPENED TO THE WILLINGNESS OF COMPANIES TO INVEST AFTER THE FINANCIAL CRISIS? EVIDENCE FROM LATIN AMERICAN COUNTRIES
Authors: Ozkan Aydin , Santillán‐Salgado Roberto J. , Yildiz Yilmaz , del Rocío Vega Zavala María
Published: February 2020

In this article we investigate the changes in corporate investment dynamics in the aftermath of the global financial crisis. Using firm‐level data from six Latin American countries from 2002 to 2015, we show that firms are less constrained and have greater ability to invest after the crisis. However, the willingness of firms to invest optimally is reduced. This is supported by strong evidence that during the postcrisis period investment–cash flow sensitivity disappears, investment‐q sensitivity increases, and the estimated speeds of adjustment for target investment decrease. Moreover, after the crisis, firms notably increase their efforts to attain optimal cash and leverage levels. Our analysis implies that firms may not always be willing to invest optimally. The willingness to invest optimally appears to be time variant and moves together with the dynamics of cash and leverage policies, albeit in opposite directions.
Near‐infrared reflectance spectroscopy based online moisture measurement in copra
Authors: Lakshmanan Madan Kumar , Chinnu Tharmalingam , Arvamuthan Gopal
Published: February 2020

Moisture in raw Copra (dried mature coconut) is an important quality parameter in the process of extraction of Coconut oil. The online and instantaneous measurement of moisture in copra chips with Near‐Infrared Reflectance Spectroscopy (NIRS) has been explored in this work. To do so, a NIRS moisture sensor with in‐house designed wireless backhaul network was commissioned at an industrial‐scale oil mill in Southern India. The accuracy of the results was validated with laboratory‐tested values. Furthermore, a chemometric analysis of NIRS signals captured from copra samples was carried out to accurately measure the moisture content. The moisture sensor was interfaced with a Supervisory Control and Data Acquisition (SCADA) system through a wireless communication network designed and developed in‐house. The system was trialed for 13 months. The system enabled for monitoring the process parameters of the oil extraction process from a safe and convenient distance away from critical instruments. The moisture content values predicted by the online NIRS sensors closely matched laboratory values (over 70% of the data was within the standard allowable tolerances). The system enabled for smarter operation, aided in improving process capability, reduced manpower, and energy requirements.

Practical Applications

The moisture content of the copra plays a crucial role in the oil extraction process and drives the market price of copra. Typically, moisture content of <7% is acceptable to the industry. High moisture content can make the copra vulnerable to fungal and pestilential attack. The in‐situ and online measurement of moisture can help improve the process of extraction of oil by considering optimum moisture and temperature. Through this process, the oil extraction efficiency and yield can be increased. By adaptively adjusting the temperature of the cooker, the energy requirements of running the plant are also optimized.
Optimizing pink‐beam fast X‐ray microtomography for multiphase flow in 3D porous media
Authors: MEISENHEIMER D.E. , RIVERS M.L. , WILDENSCHILD D.
Published: February 2020

A fast pink‐beam X‐ray microtomography methodology was developed at the GSECARS 13‐BMD beamline at the Advanced Photon Source to study multiphase flow in porous media. The white beam X‐ray distribution of the Advanced Photon Source is modified using a 1‐mm copper filter and the beam is reflected off a platinum mirror angled at 1.5 mrad, resulting in a pink beam with X‐ray intensities predominately in the range of 40–60 keV. Bubble formation in the wetting phase and wettability alteration of the solid phase from x‐ray exposure can be a problem with high flux and high energy beams, but the suggested pink‐beam configuration mitigates these effects. With a 14‐second acquisition time for capturing a complete dataset, the evolving fluid‐fronts of nonequilibrium three‐dimensional multiphase flow can be studied in real‐time and the images contain adequate image contrast and quality to measure important multiphase quantities such as contact angles and interfacial areas.

Lay Description

Understanding how fluids are transported through porous materials is pertinent to many important societal processes in the environment (e.g. groundwater flow for drinking water) and industry (e.g. drying of industrial materials such as pulp and paper). To develop accurate models and theories of this fluid transportation, experiments need to track fluids in 3‐dimensions quickly. This is difficult to do as most materials are opaque and therefore cameras cannot capture fluid movement directly. But, with the help of x‐rays, scientists can track fluids in 3D using an imaging technique called x‐ray microtomography (μCT). Standard μCT takes about 15 minutes for one image which can produce blurry images if fluids are flowing quickly through the material. We present a technique, fast μCT, which uses a larger spectrum of x‐rays than the standard technique and acquires a 3D image in 14 seconds. With the large amount of x‐rays utilized in this technique, bubbles can start to form in the fluids from x‐ray exposure. We optimized the utilized x‐ray spectrum to limit bubble formation while still achieving a rapid 3D image acquisition that has adequate image quality and contrast. With this technique, scientists can study fluid transport in 3D porous materials in near real‐time for the improvement of models used to ensure public and environmental health.
A comparison of the associations of Reid Colposcopic Index and Swede Score with cervical histology
Authors: Suwanthananon Catthaleya , Inthasorn Perapong
Published: February 2020

Aim

Cervical cancer, the fourth most common cancer in women, is preventable. Colposcopy and colposcopic scoring systems are helpful tools to guide the treatment of precancerous lesions. This study was done to compare the association between Reid colposcopic index (RCI) and Swede score.

Methods

This prospective study enrolled 159 subjects aged 18 years or over with abnormal pap smears or high‐risk HPV (types 16 and/or 18). All women underwent colposcopies, and the findings were classified by RCI and Swede score. Biopsies were done in all cases. The performance of both scores was evaluated.

Results

A total of 43 (27.0%) high‐grade lesions were detected. AUC of ROC of both tests showed excellent performance with 0.906 for RCI and 0.902 for Swede score. The correlation coefficient was 0.986. At a cutoff of 5, RCI had a sensitivity, specificity, positive predictive value, and negative predictive value for detected CIN2+ lesions of 83.7%, 89.7%, 75.0%, and 93.7%, respectively. At a cutoff of 7 for RCI score, the corresponding figures were 46.5%, 99.1%, 95.2%, and 83.3%. At a cutoff of 5, Swede score had a sensitivity, specificity, positive predictive value, and negative predictive value of 88.4%, 87.1%, 71.7%, and 95.3%. At a cutoff of 9 for Swede score, those values were 14.0%, 99.1%, 85.7%, and 75.7%.

Conclusion

There was a good association between RCI and Swede score. Both scoring systems had the good performance. Swede score is effective for practical use and applied in Thailand.
Therapeutic potential of combination therapy of soluble VEGF receptor 1 and conventional chemotherapy for ovarian cancer growth
Authors: Sato Noriko , Kumasawa Keiichi , Yamashita Michiko , Miyake Tatsuya , Nakamura Hitomi , Kimura Tadashi
Published: February 2020

Aim

This study aimed at evaluating the additional anti‐tumor effects of exogenous rVEGFR1 (sFlt1) on conventional chemotherapy in ovarian cancer cell lines.

Methods

We utilized cells from two ovarian cancer cell lines, SKOV3 and HeyA8, and treated them with a combination of rVEGFR1 (sFlt1) and carboplatin as well as rVEGFR1 (sFlt1) alone. First, we evaluated cell survival after treatment by using cell counting and MTS assays. Next, we performed Ki67 staining for evaluating the inhibitory effects of the treatment on cell proliferation, and a lactate dehydrogenase (LDH) assay for evaluating cytotoxicity. Finally, to determine whether MAP kinase signaling is involved in this process, we performed western blot analysis of extracellular signal‐regulated kinase (ERK), phospho‐ERK, c‐jun n‐terminal kinase (JNK) and phospho‐JNK.

Results

The cytotoxic and growth‐restriction effects were more pronounced in the group co‐administered with rVEGFR1 (sFlt1) and carboplatin than in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. Quantitative analysis of Ki67‐positive cells also showed a decreased proportion of Ki67‐positive cells in SKOV3 cells treated with a combination of exogeneous rVEGFR1 (sFlt1) and carboplatin compared to that in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. In the LDH assay, we also found significantly enhanced cell toxicity from the combination therapy. Finally, western blotting analysis showed that the MAPK signaling pathway was not affected by sFlt1 treatment.

Conclusion

This study confirmed the additive effects of rVEGFR1 (sFlt1) combined with conventional chemotherapy for ovarian cancer growth in in vitro assays, thus suggesting the combination of rVEGFR1 (sFlt1) and carboplatin as a potential novel therapeutic option for ovarian cancer.