bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated care programme in London: qualitative evaluation
Authors: Round Thomas , Ashworth Mark , Crilly Tessa , Ferlie Ewan , Wolfe Charles
Published: June 2018

Purpose

A well-funded, four-year integrated care programme was implemented in south London. The programme attempted to integrate care across primary, acute, community, mental health and social care. The purpose of this paper is to reduce hospital admissions and nursing home placements. Programme evaluation aimed to identify what worked well and what did not; lessons learnt; the value of integrated care investment.

Design/methodology/approach

Qualitative data were obtained from documentary analysis, stakeholder interviews, focus groups and observational data from programme meetings. Framework analysis was applied to stakeholder interview and focus group data in order to generate themes.

Findings

The integrated care project had not delivered expected radical reductions in hospital or nursing home utilisation. In response, the scheme was reformulated to focus on feasible service integration. Other benefits emerged, particularly system transformation. Nine themes emerged: shared vision/case for change; interventions; leadership; relationships; organisational structures and governance; citizens and patients; evaluation and monitoring; macro level. Each theme was interpreted in terms of “successes”, “challenges” and “lessons learnt”.

Research limitations/implications

Evaluation was hampered by lack of a clear evaluation strategy from programme inception to conclusion, and of the evidence required to corroborate claims of benefit.

Practical implications

Key lessons learnt included: importance of strong clinical leadership, shared ownership and inbuilt evaluation.

Originality/value

Primary care was a key player in the integrated care programme. Initial resistance delayed implementation and related to concerns about vertical integration and scepticism about unrealistic goals. A focus on clinical care and shared ownership contributed to eventual system transformation.
BYOD-related innovations and organizational change for entrepreneurs and their employees in SMEs
Authors: Baillette Paméla , Barlette Yves
Published: June 2018

Purpose

The purpose of this paper is to present the benefits and potential dangers of “bring your own device” (BYOD)-related practices. The paper aims to highlight new risks stemming from BYOD adoption and identifies different security paradoxes arising for entrepreneurs and their employees in the context of small- and medium-sized enterprises (SMEs).

Design/methodology/approach

A theoretical approach is proposed in this paper. As technology is an important driver of organizational change, technological innovations entail new work practices and in turn lead to a twofold “security paradox.”

Findings

This paper introduces the stakes and issues associated with BYOD-related mobile technologies. Evidence is provided that this phenomenon must be cautiously addressed to not only seize related benefits but also reduce related risks. Avenues for future research are offered to complement this work.

Practical implications

The main practical interest is to make entrepreneurs of SMEs and their employees aware of the BYOD phenomenon and its related risks and benefits.

Originality/value

From a theoretical perspective, very little work has been published in the field of management sciences about the benefits and dangers associated with the introduction of BYOD among entrepreneurs and employees in SMEs. Moreover, this study identifies a twofold “security paradox” related to information security that has never been studied in work settings.
“Brand play” versus “Brand attack”: the subversion of brand meaning in non-collaborative co-creation by professional artists and consumer activists
Authors: Kristal Samuel , Baumgarth Carsten , Henseler Jörg
Published: June 2018

Purpose

This paper aims to investigate the ways in which “non-collaborative co-creation” can affect brand equity as perceived by independent observers. It reports a study of the different effects on that perception attributable to non-collaborative co-creation that takes the form of either “brand play” or “brand attack” and is executed either by established artists or mainstream consumers.

Design/methodology/approach

A 2 × 2 between-subjects experiment (brand play versus brand attack; consumer versus artist) measured observers’ perception of brand equity before and after exposure to purpose-designed co-created treatments.

Findings

Non-collaborative co-creation has a negative effect on observers’ perceptions of brand equity and brand attack, causing a stronger dilution of brand equity than brand play. Artists either mitigate the dilution or have a positive effect on those perceptions.

Research limitations/implications

Future research could usefully investigate the relative susceptibility of brands to non-collaborative co-creation, the effects on brands of higher complexity than those in our experiment, exposed in higher-involvement media, and the effects of more diverse forms of co-creation.

Practical implications

Brand managers must recognise that co-creation carries considerable risks for brand equity. They should closely monitor and track the first signs of non-collaborative co-creation in progress. It could be beneficial to recruit artists as co-creators of controlled brand play.

Originality/value

This study offers a more complete insight into the effect of non-collaborative co-creation on observers’ perceptions of brand equity than so far offered by the existing literature. It connects the fields of brand management and the arts by investigating the role and impact of artists as collaborative or non-collaborative co-creators of brand equity.
Restorative practices and the integration of social emotional learning as a path to positive school climates
Authors: Hulvershorn Kristina , Mulholland Shaila
Published: June 2018

Purpose

An understanding of the effects of zero tolerance policies in schools has resulted in rethinking of approaches to prevent conflict and creating a healthy school climate. Restorative practices (RP) have been looked to as an alternative to zero tolerance policies. At the same time, social emotional learning (SEL) programming has been implemented to provide students with the skills to communicate and build relationships with peers. The purpose of this paper is to provide a look at the historical context shaping the development of RP, and explore connections between RP and SEL. Considerations for implementation and conceptual models for implementing RP are also discussed.

Design/methodology/approach

Informed by education policy analysis methods, this essay places RP in their broader context, explores RP and considers such practices important to study due to the unintended effects stemming from “traditional” obedience-oriented punitive approaches to school discipline (American Psychological Association Zero Tolerance Task Force, 2008; O’Malley and Austin, 2014).

Findings

Based on the analysis of current research, the authors explain that when RP are implemented with SEL programming, it is an opportunity for educational practitioners to address issues around race, gender, disability, and other aspects of diversity. By integrating these approaches together, RP become a vehicle to develop students’ SEL skills, which includes communication skills, kindness, empathy, and caring.

Research limitations/implications

An understanding of how zero tolerance policies have played out in the school setting has resulted in rethinking of current approaches to preventing conflict. Subsequently, educational leaders and professional associations have led a shift toward alternative models and practices in school discipline.

Practical implications

District, state, and federal policymakers have pressed for more constructive alternatives that foster a productive and healthy instructional climate without depriving large numbers of students the opportunity to learn (Skiba and Losen, 2016, p. 4). These approaches include RP, as well as integrating SEL into school practices and the curriculum.

Social implications

Several challenges and opportunities lie ahead. Based on the firsthand work with schools and districts implementing restorative and SEL practices, as well as the knowledge and insights gained from this analysis of research, one important need to consider is the need to integrate school disciplinary practices, including RP, into the school context and existing structures.

Originality/value

By conducting this study of the research evidence on RP, the authors were able to gain insights into questions, including: How have school practitioners applied RP as an alternative to zero tolerance policies?
An enterprising phoenix: materiality, affect and learning
Authors: Rooney Donna , Manidis Marie , Price Oriana M. , Scheeres Hermine
Published: June 2018

Purpose

The purpose of this paper is to explore how workers experience planned and unplanned change(s), how the effects of change endure in organizations and the entanglement (Gherardi, 2015) of materiality, affect and learning.

Design/methodology/approach

Research design is ethnographic in nature and draws from 30 semi-structured interviews of workers in an Australian organization. Interviews were designed to elicit narrative accounts (stories) of challenges and change faced by the workers. Desktop research of organizational documents and material artefacts complemented interview data. Analysis is informed by socio-material understandings and, in particular, the ideas of materiality, affect and learning.

Findings

Change, in the form of a fire, triggered spontaneous and surprisingly positive affectual and organizational outcomes that exceeded earlier attempts at restructuring work. In the wake of the material tragedy of the fire in one organization, what emerged was a shift in the workers and the practices of the organization. Their accounts emphasized challenges, excitement and renewal, which prompt reconsideration of learning at work, in particular the entanglement of affect, materiality and learning in times of change.

Originality/value

Much workplace learning research identifies change as conducive to learning. This paper builds on this research by providing new understandings of, and insights into, the enduring effects of change.
Impact of programs on competency, career, and income on management graduates
Authors: Paixão Roberto Brazileiro , Souza Márcio Arcanjo de
Published: June 2018

Purpose

This paper aims to evaluate the impact of Federal University of Bahia’s Business Administration graduate programs on graduates’ competency, career and income development.

Design/methodology/approach

It is a descriptive study, for which a survey was applied and the data were analyzed using quantitative techniques (descriptive analysis, factorial analysis, t-test, Mann–Whitney test and regression analysis). Data collection was conducted through an electronic questionnaire sent to the graduates in the period between 1998 and 2012.

Findings

The results show that in general, the research participants perceive competency, career and income development after the course. At the same time, a comparison between the graduates of academic and professional axes (courses) was carried out, and in general, there is a certain similarity between perceptions.

Originality/value

This research contributes to the theoretical field on evaluation of graduates, both from a methodological point of view, because of conducted statistical analysis that is complementary to other methods used, and from a practical point of view, as it offers redesign and improvement elements to the program’s curricula and teaching-learning methodologies so that it can maximize competency development, career and income of graduates.
Antecedents of turnover in federal public administration
Authors: Cavalcanti G. Ferreira Pedro , Rabelo Neiva Elaine
Published: June 2018

Purpose

Understanding the reasons that lead civil servants to abandon their offices is an important step towards qualifying personnel management in the Federal Administration. The purpose of this study is to present an initial approach to the subject and to investigate variables that favor or reduce the turnover intention among civil servants in the Federal Executive Branch.

Design/methodology/approach

To fulfill the objective stated, the study resorted to variables of values, expectations and affective commitment to the organization. Variables were tested in a model of structural equations capable of verifying if these are antecedent or not of the turnover intention levels in a sample comprising 228 civil servants.

Findings

The validation of a model of structural equations unveiled a statistically relevant relation of dependence among values, expectations and the affective commitment to the organization. Moreover, engagement proved to be a mediator of the relation between the other variables and the turnover intention.

Originality/value

The work contributed to literature by presenting evidence that low expectations among civil servants bring low affective commitment which, in turn, leads to higher willingness to quit organizations. On the other hand, the same model showed that self-transcendent values, typical to the public career (serve the public), prevail among civil servants and positively impact commitment. This scenario shows that in people management all these elements of values and expectations must be worked on to reduce the number of civil servants that quit the government every year, as well as the high costs associated with quitting.
Effect of weft yarn twist level on thermal comfort of 100 per cent cotton woven fabrics
Authors: Atalie Desalegn , Tesema Addisu Ferede , Rotich Gideon K.
Published: June 2018

Purpose

Fabrics’ thermal properties greatly influence human comfort during wear. For this reason, fabrics with optimum thermal properties need to be developed. This paper aims to investigate the effect of weft yarn twist levels on thermal and surface properties of 100 per cent cotton woven fabrics.

Design/methodology/approach

Five types of plain woven cotton fabrics were manufactured using weft yarns with 900, 905, 910, 915 and 920 twists/meter (Tpm). The other parameters of the samples as count, thread density and fabric structures were kept constant. Fabric thermal properties were evaluated by measuring its thermal conductivity, thermal resistance, actual insulation, water permeability, air permeability and wicking ability. The fabric compression and surface properties were also evaluated because they contribute to the overall clothing comfort.

Findings

The results showed that actual insulation and thermal resistance property decreased with an increase in twists/meter of the weft yarn. However, thermal conductivity does not significantly change while fabric compression reduced with an increase in twist as the surface roughness increased.

Originality/value

Comfort is a fundamental requirement in human daily existence, and it is greatly influenced by clothing, which comes in close contact with the human skin. Fabrics’ thermal properties greatly influence human comfort during wear. For this reason, fabrics with optimum thermal properties need to be developed.
The Russian tourism and hospitality market: new challenges and destinations
Authors: Sheresheva Marina Y.
Published: June 2018

Purpose

This paper aims to review recent developments in the Russian tourism and hospitality market and to underline Russia’s strong tourism prospects – despite the challenges it has to face.

Design/methodology/approach

The study sets the scene for the theme issue (that draws from both academia and industry) by discussing the challenges facing the contemporary Russian tourism and hospitality market. It also profiles the efforts of the Russian Government to boost tourism development in different Russian regions that are potentially attractive tourist destinations due to their natural resources and cultural heritage.

Findings

The paper sheds light on the major shift to domestic tourism that is partly due to the turbulent economic environment that is forcing Russia to search for internal sources of development. At the same time, the decision to rely on diversity of opportunities and sustainable regional tourism makes it possible to have a broad variety of tourist value propositions in almost all parts of Russia. This also makes Russia more attractive to foreign tourists. Still, to make Russia a popular destination internationally, improvement in almost all elements of the Russian tourist product is needed.

Originality/value

This theme issue provides an analysis and evaluation of tourism development in Russia in the current decade and, in so doing, contributes to knowledge of the fast developing Russian tourism and hospitality market by unveiling a number of new tourist products and destinations in different Russian regions.
Grandstanding and New Stock Speculation: Evidence from Private Venture Capitals in China
Authors: Wu Long , Xu Lei
Published: June 2018

Reputation is of vital importance to venture capitals (VCs). Emerging young VCs may have more incentives to grandstand through initial public offerings (IPOs) in the stock market. We examine grandstanding and IPOs on the Shanghai and Shenzhen stock exchanges between 5 June 2006 and 10 May 2012 when deregulation allows explosive growth of VCs in China. We find that grandstanding is mainly by the private VCs and has noticeable impact on the two stock exchanges. Furthermore, private VCs heavily grandstand through speculation of newly listed stocks rather than through underpricing among early IPOs. Joint investment by private and non‐private VCs may effectively inhibit the speculation of new stocks. Our findings have policy implications in the largest emerging market's context.
The transformative role of interaction rituals within therapeutic communities
Authors: Clarke Jenelle M. , Waring Justin
Published: June 2018

Mental health settings are fraught with emotion as clients address difficult life experiences and relational patterns. Clients spend a substantial amount of time together outside of structured therapy, but little is known about how these moments are potentially therapeutic, especially as sites of emotional change. We draw on interaction ritual chain theory to explore how negative emotions in situations outside of formal therapy can be transformed into positive emotions and facilitate personal change. The research is based upon a narrative ethnography of two therapeutic communities for individuals with a diagnosis of personality disorder. Despite the presence of negative transient emotions in these rituals, clients experienced positive feelings of solidarity and belonging, and the majority of clients reported increased feelings of confidence and positive change. Conversely, dynamics between clients showed clients were not always supportive of one another and at times, could exclude others, resulting in isolation and alienation. We argue interactions that generate feelings of inclusion or exclusion over time are a key component in whether clients gain positive or negative emotional feeling and experience personal change.
Matching and Regression to the Mean in Difference‐in‐Differences Analysis
Authors: Daw Jamie R. , Hatfield Laura A.
Published: June 2018

Objective

To demonstrate regression to the mean bias introduced by matching on preperiod variables in difference‐in‐differences studies.

Data Sources

Simulated data.

Study Design

We performed a Monte Carlo simulation to estimate the effect of a placebo intervention on simulated longitudinal data for units in treatment and control groups using unmatched and matched difference‐in‐differences analyses. We varied the preperiod level and trend differences between the treatment and control groups, and the serial correlation of the matching variables. We assessed estimator bias as the mean absolute deviation of estimated program effects from the true value of zero.

Principal Findings

When preperiod outcome level is correlated with treatment assignment, an unmatched analysis is unbiased, but matching units on preperiod outcome levels produces biased estimates. The bias increases with greater preperiod level differences and weaker serial correlation in the outcome. This problem extends to matching on preperiod level of a time‐varying covariate. When treatment assignment is correlated with preperiod trend only, the unmatched analysis is biased, and matching units on preperiod level or trend does not introduce additional bias.

Conclusions

Researchers should be aware of the threat of regression to the mean when constructing matched samples for difference‐in‐differences. We provide guidance on when to incorporate matching in this study design.
Procurement with Asymmetric Information About Fixed and Variable Costs
Authors: ANTLE RICK , BOGETOFT PETER
Published: June 2018

We investigate optimal rationing of resources and organizational slack when a principal procures from an agent with private information about fixed and variable costs. We study the problem in a two‐period setting with persistent types and investigate how the optimal rationing and slack depend on whether production increases or decreases over time. We find that rationing in a dynamic model with persistent types is extra costly, since the types that are eliminated in period 1 might have been attractive in period 2. The cost of rationing increases with the variability of production. If production levels are increasing (decreasing), the principal will be cautious when eliminating types with low variable (fixed) costs in period 1, since these types are particularly profitable in period 2. When production is more stable over time, harsher rationing can be applied in period 1, followed by less harsh rationing, if any, in period 2.
The Fall of Thomas Howard, 1st Earl of Suffolk and the Revival of Impeachment in the Parliament of 1621
Authors: Thrush Andrew
Published: June 2018

The revival of impeachment in 1621 has tended to be viewed exclusively through the prism of parliament. However, this article, which builds on the work of Professor Allen Horstman, suggests that a key factor in impeachment's revival was the dismissal of Lord Treasurer Suffolk for corruption in 1618. Suffolk's removal caused widespread disquiet, since it was assumed that senior officials held office for life. In order to silence these criticisms it proved necessary for the king not only to put Suffolk on trial but also to justify by precedent the lord treasurer's removal. This latter task was performed by the former lord chief justice, Sir Edward Coke, himself not long disgraced, whose researches in the medieval parliamentary record revealed the following year that errant crown ministers had hitherto been held to account by means of impeachment. Coke subsequently put this discovery to good effect when parliament met in 1621. Against the backdrop of mounting criticism against his hated rival, the lord chancellor, Francis Bacon, Coke revealed the existence of impeachment to the house of commons, whose attention was then focused on finding a way to punish the monopolists, Sir Giles Mompesson and Sir Francis Michell. In so doing, Coke not only aided the lower House, which had been struggling since 1610 to find a way of punishing non‐members, but also sought to settle an old score.
British Lobbying in Newspaper and Parliamentary Discourse, 1800–1950
Authors: McGrath Conor
Published: June 2018

Lobbying is a significant component of the modern politics industry in Britain, but we know relatively little about its historical origins and evolution. This article draws on parliamentary debates and three databases which together account for 51 newspaper titles, in order to explore how lobbying was discussed in parliament and the media between 1800 and 1950, and to gauge the growing professionalisation of lobbying. Perceptions of lobbying became somewhat less negative over the period; there are relatively few reports or allegations of corruption associated with lobbying; and lobbying by the railway industry seems to have been less substantial, while public sector lobbying was more significant, than is commonly supposed. Direct advocacy with policymakers is overwhelmingly the dominant tactic used by lobbyists of the period, with few reports of coalitions or grass‐roots campaigns. Particular concerns were expressed about the influence of lobbying around private bills. While lobbying back‐bench MPs and parliamentary committees (rather than ministers and civil servants) accounted for over 80% of the activity revealed across the whole period, there are signs by the middle of the 20th century that the focus of lobbyists is beginning to turn away from Westminster and towards Whitehall. The article paints a detailed view of the scale, scope, and significance of lobbying as it was developing into a national and systematic industry.
A Biographical Note on James Maxwell, Gentleman Usher of the Black Rod
Authors: Sainty J.C.
Published: June 2018

This note seeks to clarify the course of the career of James Maxwell, gentleman usher of the black rod in several earlier Stuart parliaments. Maxwell was a Scot who followed James I south in 1603, serving in his household and that of Charles I, first as a gentleman usher daily waiter, and from 1619 as a groom of the bedchamber. In 1620 he secured the office of black rod. In 1642 he failed to follow the king to Oxford but remained with the parliament at Westminster, although largely delegating his duties as black rod to his associate, Alexander Thayne. In 1647, he was allowed by parliament to attend the king at Holdenby House. He died in 1650 as earl of Dirletoun in Scotland, although the circumstances in which he acquired this title are obscure.
The Impact of Alcohol Use on Frontal White Matter in HIV
Authors: Gullett Joseph M. , Lamb Damon G. , Porges Eric , Woods Adam J. , Rieke Jake , Thompson Paul , Jahanshad Neda , Nir Talia M. , Tashima Karen , Cohen Ronald A.
Published: June 2018

Background

Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain.

Methods

Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease‐specific variables, and reported substance use.

Results

Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age‐adjusted HIV infection length.

Conclusions

This study provides evidence of HIV‐related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age‐adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.
Regional Patterns of Alcohol‐Induced Neuronal Loss Depend on Genetics: Implications for Fetal Alcohol Spectrum Disorder
Authors: Todd Dylan , Bonthius Daniel J. , Sabalo Lia Marie , Roghair Jasmine , Karacay Bahri , Bousquet Samantha Larimer , Bonthius Daniel J.
Published: June 2018

Background

Alcohol exposure during pregnancy can kill developing neurons and lead to fetal alcohol spectrum disorder (FASD). However, affected individuals differ in their regional patterns of alcohol‐induced neuropathology. Because neuroprotective genes are expressed in spatially selective ways, their mutation could increase the vulnerability of some brain regions, but not others, to alcohol teratogenicity. The objective of this study was to determine whether a null mutation of neuronal nitric oxide synthase (nNOS) can increase the vulnerability of some brain regions, but not others, to alcohol‐induced neuronal losses.

Methods

Immunohistochemistry identified brain regions in which nNOS is present or absent throughout postnatal development. Mice genetically deficient for nNOS (nNOS−/−) and wild‐type controls received alcohol (0.0, 2.2, or 4.4 mg/g/d) over postnatal days (PD) 4 to 9. Mice were sacrificed in adulthood (~PD 115), and surviving neurons in the olfactory bulb granular layer and brain stem facial nucleus were quantified stereologically.

Results

nNOS was expressed throughout postnatal development in olfactory bulb granule cells but was never expressed in the facial nucleus. In wild‐type mice, alcohol reduced neuronal survival to similar degrees in both cell populations. However, null mutation of nNOS more than doubled alcohol‐induced cell death in the olfactory bulb granule cells, while the mutation had no effect on the facial nucleus neurons. As a result, in nNOS−/− mice, alcohol caused substantially more cell loss in the olfactory bulb than in the facial nucleus.

Conclusions

Mutation of the nNOS gene substantially increases vulnerability to alcohol‐induced cell loss in a brain region where the gene is expressed (olfactory bulb), but not in a separate brain region, where the gene is not expressed (facial nucleus). Thus, differences in genotype may explain why some individuals are vulnerable to FASD, while others are not, and may determine the specific patterns of neuropathology in children with FASD.
Stem cell characteristics and the therapeutic potential of amniotic epithelial cells
Authors: Miki Toshio
Published: June 2018

Multiple stem cell types can be isolated from the human placenta. Recent advances in stem cell biology have revealed that human amniotic epithelial cells (hAECs) are one of the perinatal stem cells which possess embryonic stem cell‐like differentiation capability and adult stem cell‐like immunomodulatory properties. Unlike other types of placental stem cells,hAECs are derived from pluripotent epiblasts and maintain multilineage differentiation potential throughout gestation. Similar to mesenchymal stem cells,hAECs are also able to modulate the local immune response. These, and other properties, makehAECs attractive for cellular therapy. This review article summarizes current knowledge of stem cell characteristics and immunomodulatory properties of amniotic epithelial cells and aims to advance our understanding towards the goal of novel therapy development.
Are high‐ and low‐molecular‐weight sensitizing agents associated with different clinical phenotypes of occupational asthma?
Authors: Vandenplas Olivier , Godet Julien , Hurdubaea Laura , Rifflart Catherine , Suojalehto Hille , Wiszniewska Marta , Munoz Xavier , Sastre Joaquin , Klusackova Pavlina , Moore Vicky , Merget Rolf , Talini Donatella , Svanes Cecilie , Mason Paola , dell'Omo Marco , Cullinan Paul , Moscato Gianna , Quirce Santiago , Hoyle Jennifer , Sherson David L. , Kauppi Paula , Preisser Alexandra , Meyer Nicolas , de Blay Frédéric ,   European network for the PHenotyping of OCcupational ASthma (E‐PHOCAS) investigators
Published: June 2018

Background

High‐molecular‐weight (HMW) proteins and low‐molecular‐weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles.

Methods

Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n = 544) and LMW (n = 635) agents.

Results

Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work‐related rhinitis (OR [95% CI]: 4.79 [3.28‐7.12]), conjunctivitis (2.13 [1.52‐2.98]), atopy (1.49 [1.09‐2.05]), and early asthmatic reactions (2.86 [1.98‐4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59‐3.03]), daily sputum (1.69 [1.19‐2.38]), and late asthmatic reactions (1.52 [1.09‐2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07‐2.91]), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01‐1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide.

Conclusion

This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.
Maternal mortality in Italy: Results and perspectives of record‐linkage analysis
Authors: Donati Serena , Maraschini Alice , Lega Ilaria , D'Aloja Paola , Buoncristiano Marta , Manno Valerio ,   The Regional Maternal Mortality Working Group
Published: June 2018

Introduction

Accurate estimates and reliable classification of maternal deaths are imperative steps in the chain of actions targeted at reducing avoidable maternal mortality. The aims of this study were to estimate the maternal mortality ratio (MMR) in 10 Italian regions covering 77% of total national births and to identify the most suitable approach to classify the causes of death.

Material and methods

Deaths during and within 1 year after pregnancy have been identified through linkage between death registry and hospital discharge database. Regional and national data sources from 2006 to 2012 were used. The MMR has been estimated and deaths were classified as direct or indirect and according to their primary causes.

Results

A total of 277 maternal deaths within 42 days after pregnancy were identified: 149 direct, 102 indirect causes and 26 unclassified‐resulting in a MMR of 9.18 per 100 000 live births. The under‐reporting rate of official MMR figures in the participating regions is 60.3%. Hemorrhage (MMR 1.92), hypertensive disorders of pregnancy and cardiac diseases (MMR 1.06) were the leading causes of deaths occurring within 42 days after pregnancy, whereas malignancy (39%) and violent deaths (17%) were the most frequent of the 543 late maternal deaths.

Conclusions

Record‐linkage is an efficient and reliable method to estimate maternal mortality and to identify causes of maternal deaths. Both the indirect/direct and the classification by primary cause have a role in countries where direct deaths exceed indirect maternal mortality. Building upon linkage data, confidential enquiries further increase the likelihood of reducing maternal mortality.
Acid suppression medications reduce risk of oesophageal adenocarcinoma in Barrett's oesophagus: a nested case‐control study in US male veterans
Authors: Tan M. C. , El‐Serag H. B. , Yu X. , Thrift A. P.
Published: June 2018

Background

Proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) may reduce the risk of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus; however, current epidemiologic studies are inconclusive.

Aim

To evaluate the independent effects of PPIs and H2RAs on risk of OAC in patients with Barrett's oesophagus.

Methods

We conducted a nested case‐control study of male veterans diagnosed with Barrett's oesophagus. Cases with incident OAC were matched by incidence density sampling on birth year and Barrett's diagnosis date to controls with Barrett's oesophagus who did not develop OAC. We identified prescription medication usage 1 year prior to Barrett's oesophagus diagnosis to 3 months prior to the OAC diagnosis. Odds ratios (OR) and 95% CI were estimated using conditional logistic regression.

Results

Compared with 798 controls, the 300 cases were less likely to use PPIs (90.0% vs 94.5%, P = 0.01) and H2RAs (19.7% vs 25.7%, P = 0.04). In the multivariable model including the use of statins, H2RAs, aspirin and nonsteroidal anti‐inflammatory drugs, PPI use was associated with 41% lower risk of OAC (OR 0.59, 95% CI 0.35‐0.99). While risk reduction of OAC was stronger for high‐dose PPIs (omeprazole daily dose >40 mg, adjusted OR 0.11, 95% 0.04‐0.36), we did not find a dose‐response relationship with PPI duration (P trend = 0.45). Likewise, H2RA use was independently associated with 30% lower risk of OAC (OR 0.70, 95% CI 0.50‐0.99).

Conclusion

Use of PPIs and H2RAs among patients with Barrett's oesophagus are associated with lower risk of OAC. Further clinical trials are needed to confirm this possible chemopreventive effect.
Optimization of goose breast meat tenderness by rapid ultrasound treatment using response surface methodology and artificial neural network
Authors: Zou Ye , Zhang Kun , Zhang Xin Xiao , Li Pengpeng , Zhang Muhan , Liu Fang , Sun Chong , Xu Weimin , Wang Daoying
Published: June 2018

The aim of this study was to develop a prediction model on tenderization of goose breast meat by response surface methodology (RSM) and artificial neural network (ANN). The experiments were operated on the basis of a three‐level, three‐variable (ultrasound power, ultrasound time, and storage time) Box‐Behnken experimental design. Under RSM and ANN optimum conditions, experimental Meullenet‐Owens razor shear (MORS) of meat (1862.6 g and 1869.9 g) was in reasonable agreement with predicted one. Nevertheless, better prediction capability of ANN was proved by higher R2 (0.996) and lower absolute average deviation = 4.257) compared to those for RSM (0.852 and 16.534), respectively. These results revealed that ANN was more accurate and much better than RSM model for the optimization of tenderness of meat. The optimum conditions of ultrasound power, ultrasound time, and storage time given by ANN were 812 W, 24.5 min and 25.7 hr, respectively. Under the optimized condition, the cooking loss of meat significantly decreased by ultrasound treatment compared with untreated meat. Lower cooking loss and MORS at the optimal condition were beneficial to meet the satisfaction of consumer and producers for meat factory.
Osteology of Ronquilus jordani (Zoarcoidei: Bathymasteridae), with a discussion of the developmental osteology and systematics of bathymasterid fishes
Authors: Hilton Eric J. , Stevenson Duane E. , Matarese Ann C.
Published: June 2018

The zoarcoid family Bathymasteridae contains seven species in three genera (Bathymaster, Rathbunella, Ronquilus) found in the North Pacific Ocean. Although several synapomorphies have been identified for the family, molecular analyses recover the family as a paraphyletic grade. The goals of this study are to provide a description of the skeleton of R. jordani as a baseline contribution for future systematic comparisons among all bathymasterid taxa and zoarcoids. We used our osteological study to discuss ontogenetically variable characters that appear to carry phylogenetic signal within Zoarcoidei. Finally, we discuss the systematic relationships of Bathymasteridae, including its monophyly and their systematic relationships. The vertebrae of Bathymasteridae develop in two distinct patterns. In Ronquilus and Bathymaster, the vertebrae initially form in the mid‐caudal region and development proceeds both anteriorly and posteriorly until the entire vertebral column is complete. In contrast, in Rathbunella the vertebrae initially form immediately posterior to the skull and development proceeds posteriorly; this is interpreted to be plesiomorphic. Other characters that were clarified (e.g., presence of well‐developed teeth on the gill rakers of Ronquilus) or described (e.g., variation in fusion caudal skeleton elements across Zoarcoidei) now must be evaluated in a taxonomically comprehensive systematic analysis of Zoarcoidei.
Sevoflurane Impairs Insulin Secretion and Tissue‐Specific Glucose Uptake In Vivo
Authors: Høyer Kasper F. , Nielsen Thomas S. , Risis Steve , Treebak Jonas T. , Jessen Niels
Published: June 2018

The use of anaesthetics severely influences substrate metabolism. This poses challenges for patients in clinical settings and for the use of animals in diabetes research. Sevoflurane can affect regulation of glucose homoeostasis at several steps, but the tissue‐specific response remains to be determined. The aim of the study was to investigate the pharmacological effect of sevoflurane anaesthesia on glucose homoeostasis during hyperinsulinaemic clamp conditions, the gold standard method for assessment of whole‐body insulin sensitivity. Conscious mice (n = 6) and mice under sevoflurane anaesthesia (n = 8) underwent a hyperinsulinaemic clamp where constant infusion of insulin and donor blood was administered during variable glucose infusion to maintain isoglycaemia. 2‐[1‐14C]‐deoxy‐D‐glucose was infused to determine tissue‐specific uptake of glucose in adipose tissue, heart, brain and skeletal muscle. Sevoflurane anaesthesia severely impaired insulin‐stimulated whole‐body glucose uptake demonstrated by a 50% lower glucose infusion rate (GIR). This was associated with decreased glucose uptake in brain, soleus, triceps and gastrocnemius muscles in sevoflurane‐anaesthetized mice compared to conscious mice. Plasma‐free fatty acids (FFA), a potent inducer of insulin resistance, increased by 42% in mice during sevoflurane anaesthesia. In addition, insulin secretion from pancreatic β‐cell was lower in fasted, anaesthetized mice. Sevoflurane anaesthesia impairs insulin secretion, induces insulin resistance in mice and reduces glucose uptake in non‐insulin‐sensitive tissue like the brain. The underlying mechanisms may involve sevoflurane‐induced mobilization of FFA.
In Vitro Screening of Six Protein Kinase Inhibitors for Time‐Dependent Inhibition of CYP2C8 and CYP3A4: Possible Implications with regard to Drug–Drug Interactions
Authors: Filppula Anne M. , Mustonen Tiffany M. , Backman Janne T.
Published: June 2018

Several protein kinase inhibitors have been reported to affect cytochrome P450 (CYP) 3A by time‐dependent inhibition. Herein, we tested a set of six kinase inhibitors for time‐dependent inhibition of CYP2C8 and CYP3A4 in human liver microsomes. Dovitinib, midostaurin and nintedanib exhibited an increased inhibition of CYP3A4 after a 30‐min. pre‐incubation with NADPH, as compared to no pre‐incubation (IC50 shift >1.5). Masitinib, trametinib and vatalanib did not affect CYP2C8 or CYP3A4 by time‐dependent inhibition (IC50 shift <1.5). The inhibitory mechanism of CYP3A4 by midostaurin and nintedanib, but not by dovitinib, was consistent with irreversible mechanism‐based inhibition. The maximal inactivation rate (kinact) and inhibitor concentration that supports half‐maximal rate of inactivation (KI) values of midostaurin and nintedanib were 0.052 1/min. and 2.72 μM, and 0.025 1/min. and 17.3 μM, respectively. According to static predictions, inactivation of CYP3A4 by nintedanib was unlikely to cause drug–drug interactions with clinically used doses of nintedanib, whereas midostaurin was predicted to increase the plasma exposure to CYP3A4‐dependent substrates several fold. Furthermore, based on reversible inhibition, masitinib and vatalanib were predicted to increase the plasma exposure to sensitive CYP2C8 and CYP3A4 substrates by ≥2‐fold. In summary, our data identify midostaurin and nintedanib as time‐dependent inhibitors of CYP3A4 and detect a risk of drug–drug interactions between vatalanib and CYP2C8 substrates, and between masitinib, midostaurin and vatalanib and CYP3A4 substrates. The liability of kinase inhibitors to affect CYP enzymes by time‐dependent inhibition may have long‐term consequences, in terms of drug–drug interactions and toxicities.
Inhibition of stromal‐interacting molecule 1‐mediated store‐operated Ca2+ entry as a novel strategy for the treatment of acquired imatinib‐resistant gastrointestinal stromal tumors
Authors: Yang Ziyi , Pan Lijia , Liu Shilei , Li Fengnan , Lv Wenjie , Shu Yijun , Dong Ping
Published: June 2018

Imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GIST); however, primary and secondary resistance to imatinib is still a major cause of treatment failure. Multiple mechanisms are involved in this progression. In the present study, we reported a novel mechanism for the acquired resistance to imatinib, which was induced by enhanced Ca2+ influx via stromal‐interacting molecule 1 (STIM1)‐mediated store‐operated Ca2+ entry (SOCE). We found that the STIM1 expression level was related to the acquired resistance to imatinib in our studied cohort. The function of STIM1 in imatinib‐resistant GIST cells was also confirmed both in vivo and in vitro. The results showed that STIM1 overexpression contributed to SOCE and drug response in imatinib‐sensitive GIST cells. Blockage of SOCE by STIM1 knockdown suppressed the proliferation of imatinib‐resistant GIST cell lines and xenografts. In addition, STIM1‐mediated SOCE exerted an antiapoptotic effect via the MEK/ERK pathway. The results from this study provide a basis for further research into potential novel therapeutic strategies in acquired imatinib‐resistant GIST.
Great Barrier Reef recovery through multiple interventions
Authors: Condie Scott A. , Plagányi Éva E. , Morello Elisabetta B. , Hock Karlo , Beeden Roger
Published: June 2018

The decline of coral cover on Australia's Great Barrier Reef (GBR) has largely been attributed to the cumulative pressures of tropical cyclones, temperature‐induced coral bleaching, and predation by crown‐of‐thorns starfish (CoTS). In such a complex system, the effectiveness of any management intervention will become apparent only over decadal time scales. Systems modeling approaches are therefore essential to formulating and testing alternative management strategies. For a network of reefs, we developed a metacommunity model that incorporated the cumulative pressures of tropical cyclones, coral bleaching, predation, and competition between corals. We then tested the response of coral cover to management interventions including catchment restoration to reduce discharge onto the reef during cyclone‐induced flood events and enhanced protection of trophic networks supporting predation of CoTS. Model results showed good agreement with long‐term monitoring of the GBR, including cyclical outbreaks of CoTS driven by predator‐prey dynamics on the network of reefs. Testing of intervention strategies showed that catchment restoration would likely improve coral cover. However, strategies that combined catchment restoration with enhanced CoTS predation were far more effective than catchment restoration alone.