bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulation of splicing-related proteins in prostate cancer is controlled by FOXA1
Authors: Foster John G. , Arkell Rebecca , Giudice Marco Del , Anene Chinedu , Lauria Andrea , Kelly John D. , Lemoine Nicholas R. , Oliviero Salvatore , Cereda Matteo , Rajan Prabhakar
Published: December 2018

Prostate cancer (PCa) is genomically driven by dysregulation of transcriptional networks involving the transcriptional factors (TFs) FOXA1, ERG, AR, and HOXB13. However, the role of these specific TFs in the regulation of alternative pre-mRNA splicing (AS), which is a proven therapeutic vulnerability for cancers driven by the TF MYC, is not described. Using transcriptomic datasets from PCa patients, we tested for an association between expression of FOXA1, ERG, AR, HOXB13, and MYC, and genes involved in AS - termed splicing-related proteins (SRPs), which have pleiotropic roles in RNA metabolism. We identified FOXA1 as the strongest predictor of dysregulated SRP gene expression, which was associated with PCa disease relapse after treatment. Subsequently, we selected a subset of FOXA1-binding and actively-transcribed SRP genes that phenocopy the FOXA1 dependency of PCa cells, and confirmed in vitro via knockdown and over-expression that FOXA1 regulates SRP gene expression. Finally, we demonstrated the persistence of a FOXA1-SRP gene association in treatment-relapsed castration-resistant PCa (CRPCa) patients. Our data demonstrate, for the first time, that FOXA1 controls dysregulated SRP gene expression, which is associated with poor PCa patient outcomes. Analogous to MYC-driven cancers, our findings implicate the therapeutic targeting of SRPs and AS in FOXA1-overexpressing PCa.
Leaders as organisational representatives: a structural model
Authors: Dartey-Baah Kwasi , Addo Seth Ayisi
Published: December 2018

Purpose

Leaders are seen as representatives of their organisations; as such, their actions and behaviours towards their subordinates reflect on the organisations. The purpose of this paper is to investigate the influence of some dimensions under transformational and transactional leadership styles on perceived organisational support (POS) in Ghana.

Design/methodology/approach

Data were collected from 264 engineers and technicians from the country’s power transmission subsector through a survey. Covariance-based structural equation modelling was used in analysing the data with the aid of Statistical Package for Social Sciences and AMOS.

Findings

The analysis indicated surprisingly that idealised influence predicted POS negatively while intellectual stimulation had no significant influence on employees’ POS. However, inspirational motivation, individualised consideration and contingent rewards predicted employees’ POS positively with contingent reward having the highest influence on POS.

Practical implications

The study’s findings indicate the importance that engineers and technicians in Ghana attach to support from their leaders, specifically inspiration and motivation, consideration for their needs and interests and rewards for their performance; thus, the study recommended that organisations must entreat their leaders to show such supportive behaviours towards their subordinates.

Originality/value

The study findings present fresh knowledge from a developing country perspective with regard to the importance that employees attach to these leadership dimensions.
Identification of critical risk factors in public-private partnership project phases in developing countries
Authors: Babatunde Solomon Olusola , Perera Srinath , Adeniyi Onaopepo
Published: December 2018

Purpose

Public‐private partnerships (PPPs) are being faced by risk threats, notwithstanding the fact that the PPP model has been structured in a way that the associated risks are shared by both the public and private sectors. Consequently, the sources of risk change over the PPP project phases. Thus, the purpose of this paper is to identify and assess the risk factors in PPP infrastructure project phases comprising development phase, construction phase, operation phase and project life cycle through an empirical approach.

Design/methodology/approach

The study adopted four different data-gathering approaches including literature review, desk review, brainstorming session and questionnaire survey. In order to capture a broad perception of stakeholders, the questionnaires were administered to three different stakeholder organizations to include public sector authorities (i.e. ministries, department and agencies), concessionaires and lenders/banks involved in different PPP infrastructure projects implementation in Nigeria. A total of 81 questionnaires were administered, out of which 63 were retrieved but after checking through the completed questionnaires, 60 questionnaires were found suitable for the analysis. Data collected were analyzed using descriptive statistics, mean score, Kruskal–Wallis test and the risk significance index in terms of severity and likelihood of occurrence conducted.

Findings

In total, 70 risk factors were identified with respect to PPP project phases and their relative importance was gauged. In addition, the analysis of total 70 risk factors in the development phase, construction phase, operation phase and project life cycle phase indicated that 51 risk factors are located in the yellow zone, which is considered as moderate and 19 risk factors are located in the red zone that are regarded as critical.

Practical implications

The identification of specific critical risk factors in each PPP project phase will provide a benchmark in developing risk management programs in developing countries.

Originality/value

These study findings would be useful for PPP stakeholders to focus their attention, priorities and leadership in managing these critical risk factors. Furthermore, the findings of this study are significant in providing an in-depth understanding of the current Nigeria’s PPP market environment, which is a true reflection of developing countries as a whole.
Views of Estonian nonprofit executives on succession: lessons from the field
Authors: Santora Joseph C. , Bozer Gil , Kooskora Mari
Published: December 2018

Purpose

The purpose of this paper is to investigate the perceptions of five leadership succession themes by executives of Estonian nonprofit organizations.

Design/methodology/approach

This is a qualitative study that uses narrative inquiry and purposive sampling. Face-to-face and Skype interviews were conducted with 15 executives.

Findings

Succession was unplanned in most of the Estonian nonprofits; successors were coached during initial transitionary periods; insiders were preferred to outsiders; requirements of executive positions were unmet because of a talent shortfall; lack of trust, unexpected behavior, and possible ethical issues were key risk factors associated with succession; and mixed opinions were received regarding the advantages and disadvantages of succession planning.

Research limitations/implications

Narrow focus on Estonian nonprofit organizations and their executives, purposive sampling, and single qualitative research method. Results may not be applicable to other nonprofits.

Practical implications

Practitioners of Estonian nonprofits can better understand the implications of executive succession issues. Lessons learned may help other nonprofit leaders.

Social implications

Having a carefully crafted succession plan can enable smoother transitions between organizational leaders and create organizational stability, thereby ensuring a continuous delivery of goods and services to clients.

Originality/value

Seminal research – this is the first study of its kind on Estonian nonprofit organizations and executive succession issues. This paper can serve as a foundation for further research on Eastern European nonprofits.
Work-family balance of female parliamentarians in Ghana
Authors: Markwei Ummu , Kubi Michael , Quao Benedicta , Attiogbe Esther Julia
Published: December 2018

Purpose

The purpose of this paper is to present the challenges female parliamentarians in Ghana face in their attempt to balance their professions and families.

Design/methodology/approach

This is a qualitative study which explores the nature of strain female MP’s in Ghana encounter in their struggle to achieve a work-life balance.

Findings

It is concluded that most female parliamentarians in Ghana go through tough times in trying to juggle career with family life. The study revealed that the MPs adopt strategies such as prioritizing roles, limiting official duties at home and using social support to help them cope with the pressures of their roles. The organizational policies put in place to aid female employees to achieve a healthy work-life balance did not yield much result for the participants in this study.

Originality/value

The originality of this paper lies in it being the first study that qualitatively explores the complex challenges female parliamentarians face in their political careers and family lives in Ghana.
Homeless medical respite service provision in the UK
Authors: Dorney-Smith Samantha , Thomson Emma , Hewett Nigel , Burridge Stan , Khan Zana
Published: December 2018

Purpose

The purpose of this paper is to review the history and current state of provision of homeless medical respite services in the UK, drawing first on the international context. The paper then articulates the need for medical respite services in the UK, and profiles some success stories. The paper then outlines the considerable challenges that currently exist in the UK, considers why some other services have failed and proffers some solutions.

Design/methodology/approach

The paper is primarily a literature review, but also offers original analysis of data and interviews, and presents new ideas from the authors. All authors have considerable experience of assessing the need for and delivering homeless medical respite services.

Findings

The paper builds on previous published information regarding need, and articulates the human rights argument for commissioning care. The paper also discusses the current complex commissioning arena, and suggests solutions.

Research limitations/implications

The literature review was not a systematic review, but was conducted by authors with considerable experience in the field. Patient data quoted are on two limited cohorts of patients, but broadly relevant. Interviews with stakeholders regarding medical respite challenges have been fairly extensive, but may not be comprehensive.

Practical implications

This paper will support those who are thinking of undertaking a needs assessment for medical respite, or commissioning a new medical respite service, to understand the key issues involved.

Social implications

This paper challenges the existing status quo regarding the need for a “cost-saving” rationale to set up these services.

Originality/value

This paper aims to be the definitive paper for anyone wishing to get an overview of this topic.
Do the rich pollute more? Mexican household consumption by income level and CO2 emissions
Authors: Santillán Vera Mónica , de la Vega Navarro Angel
Published: December 2018

Purpose

The purpose of this paper is to quantitatively examine if varying household consumption activities at different income levels drove CO2 emissions to different degrees in Mexico from 1990 to 2014.

Design/methodology/approach

The paper applied a simple expenditure-CO2 emissions elasticity model – a top-down approach – using data from consumption-based CO2 emission inventories and the “Household Income and Expenditure Survey” and assuming a range of 0.7-1.0 elasticity values.

Findings

The paper results show a large carbon inequality among income groups in Mexico throughout the period. The household consumption patterns at the highest income levels are related to significantly more total CO2 emissions (direct + indirect) than the household consumption patterns at the lowest income levels, in absolute terms, per household and per capita. In 2014, for example, the poorest household decile emitted 1.6 tCO2 per capita on average, while the wealthiest decile reached 8.6 tCO2 per capita.

Practical/implications

The results suggest that it is necessary to rethink the effect of consumption patterns on climate change and the allocation of mitigation responsibilities, thus opening up complementary options for designing mitigation strategies and policies.

Originality/value

The paper represents an alternative approach for studying CO2 emissions responsibility in Mexico from the demand side, which has been practically absent in previous studies. The paper thereby opens a way for studying and discussing climate change in terms of consumption and equity in the country.
Consumer participation in last-mile logistics service: an investigation on cognitions and affects
Authors: Wang Xueqin , Yuen Kum Fai , Wong Yiik Diew , Teo Chee-Chong
Published: December 2018

Purpose

Increasingly, the logistics industry offers innovative solutions that interact with end-consumers directly. The purpose of this paper is to examine the consumer participation behaviour in co-creating logistics service values, using self-collection via automated parcel station as an example. Built on the synthesised insights from logistics studies and behavioural theories on consumers’ attitude and affect, the effect of cognitions (what consumers think) and affects (what consumers feel) are investigated.

Design/methodology/approach

A total of 500 valid responses are collected from an online panel of respondents and the data are analysed using exploratory factor analysis and structural equation modelling.

Findings

Consumers’ affects towards participation are stronger motivations that not only intrinsically motivate consumers to participate but also exert an indirect influence via consumers’ cognitions.

Practical implications

To elicit consumers’ affections, it is critical to create enjoyable (enjoyment), assuring (assurance) and secure (security) service experiences. On the other hand, an overly straightforward service offering (in terms of cognitive functionality), void of the aforementioned experiences, may discourage consumers from participation.

Originality/value

This research unveils consumer participation in co-creating logistics service values, contributing to studies on the emerging phenomenon of consumer logistics. A rebalancing of the logistics research from a utility-creation perspective to an experience-creation perspective has been advocated.
Global-local consumer identities as drivers of global digital brand usage
Authors: Makri Katerina , Papadas Karolos-Konstantinos , Schlegelmilch Bodo B.
Published: December 2018

Purpose

The purpose of this paper is to represent the first empirical attempt to explore global-local consumer identities as drivers of global digital brand usage. Specifically, this study considers a unique category of digital products, social networking sites (SNS), and develops a set of hypotheses to assess the mechanism through which location-based identities influence the actual usage of global SNS (Facebook and Instagram). Moreover, cross-country variations are investigated under the lens of developed vs developing countries.

Design/methodology/approach

Cross-country surveys in a developed (Austria) and a developing country (Thailand) were conducted. Data collected from 425 young adults were analyzed using SEM techniques in order to test a set of hypotheses.

Findings

Results show that in Thailand, users with a global identity enjoy participating in global SNS more than their counterparts in Austria. In addition, consumers with a local identity in Thailand demonstrate less pleasure when participating in global SNS than their counterparts in Austria, and consequently are less inclined to use global SNS.

Practical implications

Findings provide digital marketers with useful insights into important strategic decisions regarding the selection and potential adaptation of global digital brands according to the country context.

Originality/value

This research is the first to extend the location-based identity research in the context of global digital brands, explain how global-local identities predict SNS usage through an engagement mechanism and investigate cross-country variations of this mechanism.
The InstaBooth: an interactive methodology for community involvement and place-making
Authors: Guaralda Mirko , Mayere Severine , Caldwell Glenda , Donovan Jared , Rittenbruch Markus
Published: December 2018

Purpose

Community involvement is a common strategy to negotiate changes to the built environment. Traditional community involvement approaches are increasingly augmented through playful elements or through the use of technology. The purpose of this paper is to present a case study of a community involvement approach aimed at expanding participants’ ability to contribute to the issue. Through the design of bespoke interactive approaches to asking questions and receiving responses, the InstaBooth shifts the involvement process toward an open discussion between community members.

Design/methodology/approach

The InstaBooth methodology established in this paper is based on the use of a physical interactive installation for situated community involvement and place-making, the InstaBooth. This methodology embeds design thinking and collaborative approaches to move the focus of the engagement from data gathering to data sharing and content co-creation.

Findings

In 2015, the authors worked with the local community of Pomona, Queensland, Australia, to inform the new masterplan for the town center by using the InstaBooth as a community involvement methodology. Examining the case of Pomona reveals how the InstaBooth approach allows participants to join a discussion about their own environment in a playful and unstructured way. This is achieved through the application of design thinking across three key phases of the community engagement; 1) planning the engagement strategy, 2) implementation of the strategy and deployment and 3) data co-analysis.

Originality/value

The InstaBooth is an interactive methodology which has allowed citizens to engage in the discussion about the future development of their town strengthening their sense of place and sense of community. The significance of this paper is applicable to others interested in community involvement and place-making, as it presents a novel methodology that combines different methods for different contexts while embedding co-creation in its approach.
Isolating small Belize banks from the global system
Authors: Duncan Philippa
Published: December 2018

Purpose

The purpose of this paper is to increase insights into the withdrawal of correspondent banks (CBs) from developing markets.

Design/methodology/approach

A case study of a small offshore bank in Belize was conducted using information collected from the bank’s CEO and compliance officer through semi-structured interviews. The interview data were triangulated with data from relevant laws in Belize and literature review.

Findings

Compliance with international standards is onerous on small banks, but necessary to level the playing field and protect the global system. Practices within small banks effectively combat money laundering, but remain unsung because size and geographic location of banks influence perceptions about the banks. The approach to de-risking was overreaching and unfair.

Research limitations/implications

The findings are specific to one offshore bank, but create awareness of Belize banking practices to mitigate money laundering risks. The results could influence regulators, international organizations and CBs to pierce through to the bank level to assess risks and determine CB relationships.

Originality/value

This is the first study providing firsthand accounts of efforts by a small Belize bank to comply with international standards and remain connected to the global financial system. The study highlights a critical weakness in employing a risk-based approach to rate banks.
Swarm intelligence approaches in supply chain management: potentials, challenges and future research directions
Authors: Soni Gunjan , Jain Vipul , Chan Felix T.S. , Niu Ben , Prakash Surya
Published: December 2018

Purpose

It is worth mentioning that in supply chain management (SCM), managerial decisions are often based on optimization of resources. Till the early 2000s, supply chain optimization problems were being addressed by conventional programming approaches such as Linear Programming, Mixed-Integer Linear Programming and Branch-and-Bound methods. However, the solution convergence in such approaches was slow. But with the advent of Swarm Intelligence (SI)-based algorithms like particle swarm optimization and ant colony optimization, a significant improvement in solution of these problems has been observed. The purpose of this paper is to present and analyze the application of SI algorithms in SCM. The analysis will eventually lead to development of a generalized SI implementation framework for optimization problems in SCM.

Design/methodology/approach

A structured state-of-the-art literature review is presented, which explores the applications of SI algorithms in SCM. It reviews 56 articles published in peer-reviewed journals since 1999 and uses several classification schemes which are critical in designing and solving a supply chain optimization problem using SI algorithms.

Findings

The paper revels growth of swarm-based algorithms and seems to be dominant among all nature-inspired algorithms. The SI algorithms have been used extensively in most of the realms of supply chain network design because of the flexibility in their design and rapid convergence. Large size problems, difficult to manage using exact algorithms could be efficiently handled using SI algorithms. A generalized framework for SI implementation in SCM is proposed which is beneficial to industry practitioners and researchers.

Originality/value

The paper proposes a generic formulation of optimization problems in distribution network design, vehicle routing, resource allocation, inventory management and supplier management areas of SCM which could be solved using SI algorithms. This review also provides a generic framework for SI implementation in supply chain network design and identifies promising emerging issues for further study in this area.
The disruptive impact of future advanced ICTs on maritime transport: a systematic review
Authors: Bălan Carmen
Published: December 2018

Purpose

This systematic literature review focuses on the following future advanced information and communication technologies (ICTs) applied in the maritime transport of cargo: Internet of Things (IoT), big data, cloud computing and autonomous ships/vessels (including unmanned ships/vessels). The review question is: “RQ: In what context and by means of what mechanism does the implementation of future advanced ICTs have disruptive impact on maritime transport?”.

Design/methodology/approach

The paper complies with the methodological requirements of systematic reviews. The information analysis and synthesis are based on the CIMO logic, referring to the context (C), intervention (I), mechanism (M) and outcome (O) of the implementation of future advanced ICTs in maritime transport.

Findings

The review identifies the contextual factors and components of the mechanism that lead to the disruptive impact of different types of future advanced ICT interventions on maritime transport.

Research limitations/implications

The review approaches only the most important future advanced ICTs that will disrupt maritime transport.

Practical implications

The maritime transport organizations should consider: intended outcome as intervention trigger; increased efficiency and responsiveness; benchmarking.

Originality/value

For the first time, the CIMO logic is applied in a systematic review focused on future advanced ICTs in maritime transport. The CIMO-DMT model is elaborated as a basis for further research. Ten directions of study are recommended in a future research agenda.
Design, simulation, fabrication and testing of ultrasonic gas flowmeter transducer (sensor)
Authors: Mousavi Seyed Foad , Hashemabadi Seyed Hassan , Azizi Moghaddam Hossein
Published: December 2018

Purpose

Invasive transit-time ultrasonic flow measurement involves the use of ultrasonic transducers, which sense the flowing fluid and are the most important parts of an ultrasonic flowmeter. In this study, two ultrasonic transducers were designed, numerically simulated and fabricated to be used in an ultrasonic gas flowmeter.

Design/methodology/approach

PZT-5H piezoceramic elements with specific dimensions were designed and used as beating heart inside the transducers. Different methods, including impedance-frequency analysis, optical emission spectroscopy and performance tests in pressurized chambers were used to evaluate the piezoelectric elements, ultrasonic transducer housings and the fabricated transducers, respectively. In addition, finite element method results showed its ability for design stages of ultrasonic transducer.

Findings

Experimental results for transit time difference (TTD) and the normalized received voltage were compared with simulation results at the same conditions. There was a quite good agreement between the two method results. Extensive simulation results showed that under the considered range of environmental conditions, the change of acoustic path length has the most impact on TTD, with respect to temperature and pressure. A change of 1 mm in acoustic path length leads to 0.74 per cent change in TTD, approximately. In addition, for normalized received voltage, 1 bar change in pressure has the most impact and its value is as high as 3.76 per cent.

Practical implications

This method is possibly used in ultrasonic gas flowmeter fabrication.

Originality/value

In this work, design, fabrication, experimental tests and numerical simulation of ultrasonic transducers are presented.
Sustaining ignorance: the uncertainties of groundwater and its extraction in the Salar de Atacama, northern Chile
Authors: Babidge Sally
Published: December 2018

The extraction of groundwater and the regulation of its use in many parts of the world have been found to present a particular kind of problem. A contest involving mining companies, an ‘impacted’ community, and the state arising from groundwater and its extraction in the Salar de Atacama, northern Chile, provides a stark example. What marks the case are the many uncertainties about underground water and the quantities extracted. This article argues that uncertainty characterizes conditions of ‘late industrialism’ and that corporate practice that sustains ignorance is a form of powerful agency that in turn maintains the conditions for potentially harmful extractive activity. Critically engaging with the proposition that water may act in the relational process of unknowing contributes to the analysis of how corporate practice may sustain ignorance. This also suggests that alternative political responses to uncertainty are possible.
Scripting development through formalization: accounting for the diffusion of village savings and loans associations in Tanzania
Authors: Green Maia
Published: December 2018

Village savings and loan associations (VSLAs) are a form of self‐organized savings association which has been successfully promoted by development agencies across the Global South. This article examines the increase in VSLAs in Tanzania through an investigation of the practices through which they are organized. Self‐organized savings associations use extreme formalization to enact the social and financial discipline which enables members to count on one another. Anthropological theories of ritual as disciplinary practice shed light on the organizational practices of savings associations and their expansion. Such associations adopt the organizational properties of ritual to generate and sustain autonomous local institutions. Ritualization has added value for systems of financial ordering as a ‘framing’ device through which the financial order of saving can be delineated. Whereas sociological theorizations of institutional diffusion perceive ritualization as empty copying, ethnographically informed anthropological analysis demonstrates the productivity of formalization where detachment from ordinary relations is a sought attribute of organization
On secularity: Marxism, reality, and the Messiah in Brazil
Authors: Lebner Ashley
Published: December 2018

On 17 April 1996, police opened fire on more than 1,500 unarmed protesters of the Landless Workers’ Movement (MST) in Southeast Pará, Brazil, killing nineteen and wounding seventy‐nine. Two years later, Osias, one of the wounded survivors, awoke to find that he had written a messianic prophecy, which he decided to share because it contained ‘a lot of reality’. This article explores what conditioned Osias's expectation that his text could provoke public reflections on reality. As such, it engages with a question unexplored by current scholarship: why the will to publicity might be inextricable from secularity, which I define as the condition of living with secularization, understood in turn not as the rise of unbelief, but as the expansion of a domain of thought and practice distinguished from religion. The ethnography ultimately inspires a rereading of Asad's Formations of the secular, interrogates assumptions about the determining reality of ‘secularism’ and ‘politics’, and makes more visible how anthropological writing is shaped by secularity. With a postscript on the October 2018 presidential elections.
Statins and risk of cataracts: A systematic review and meta‐analysis of observational studies
Authors: Alves Carlos , Mendes Diogo , Batel Marques Francisco
Published: December 2018

Introduction

Two previous meta‐analyses evaluated the risk of cataracts associated with statins, but did not include relevant studies suggesting a cataractogenic effect.

Aims

The aim of this systematic review and meta‐analysis of observational studies is to evaluate such association considering the latest published evidence.

Methods

A literature search was conducted to identify observational, comparative studies evaluating the risk of developing cataracts in patients treated with statins. A meta‐analysis was performed to estimate odds ratios (ORs). Results were stratified according to the following studies’ subgroups: design, methodological quality, method of diagnosis of cataract, patients’ age, and median follow‐up. Meta‐regressions evaluated the influence of the following risk factors: smoking, hypertension, corticosteroids, selective serotonin reuptake inhibitors (SSRI), diabetes mellitus, and cardiovascular disease.

Results

Twenty‐one studies were included. Treatment with statins was associated with an increased risk of cataracts [OR: 1.11 (95% CI: 1.02‐1.21); P = 0.017; I2 = 97.5%]. This risk remained statistically significant among case‐controls, good methodological quality studies, studies with length of follow‐up ≥5 years and those which outcome was cataract surgery. Between‐studies heterogeneity was high among all risk estimates. Meta‐regressions identified an inverse relationship between the risk of cataracts and the proportion of diabetic patients in the studies.

Conclusions

The results point out an increased risk of cataract development with statins. However, since the magnitude of the effect is low and between‐studies heterogeneity is high, the extent in which these results have impact on the benefit/risk ratio of statins is difficult to ascertain due to the uncertainty of the findings.
Finding smoking hot‐spots: a cross‐sectional survey of smoking patterns by housing tenure in England
Authors: Jackson Sarah E. , Smith Cheryll , Cheeseman Hazel , West Robert , Brown Jamie
Published: December 2018

Aims

To examine smoking prevalence, motivation and attempts to stop smoking, markers of cigarette addiction and success in quit attempts of people living in social housing in England compared with other housing tenures.

Design and setting

A large cross‐sectional survey of a representative sample of the English population conducted between January 2015 and October 2017.

Participants

A total of 57 522 adults (aged ≥ 16 years).

Measurements

Main outcomes were smoking status, number of cigarettes per day, time to first cigarette, exposure to smoking by others, motivation to stop smoking, past‐year quit attempts and use of cessation support. Covariates were age, sex, social grade, region and survey year.

Findings

Adults in social housing had twice the odds of being smokers than those living in other housing types [odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.98–2.22, P < 0.001]. Smokers in social housing consumed more cigarettes daily (adjusted mean difference = 1.09 cigarettes, 95% CI = 0.72–1.46, P < 0.001) and were more likely to smoke within 30 minutes of waking (OR = 1.63, 95% CI = 1.48–1.79, P < 0.001) than smokers living in other housing types. Prevalence of high motivation to stop smoking was similar across housing types (OR = 1.04, 95% CI = 0.91–1.19, P = 0.553). The prevalence of quit attempts and use of cessation support within the past year were greater in social compared with other housing (OR = 1.14, 95% CI = 1.03–1.26, P = 0.011; OR = 1.30, 95% CI = 1.09–1.54, P = 0.003), but success in quitting was much lower (OR = 0.57, 95% CI = 0.45–0.72, P < 0.001).

Conclusions

In England, living in social housing is a major independent risk factor for smoking. These easily identifiable hot‐spots consist of smokers who are at least as motivated to stop as other smokers, but find it more difficult.
Unilateral pigmentary retinopathy: a retrospective case series
Authors: Errera Marie‐Hélène , Robson Anthony G. , Wong Tracey , Hykin Philip G. , Pal Bishwanath , Sagoo Mandeep S. , Pavesio Carlos E. , Moore Anthony T. , Webster Andrew R. , MacLaren Robert E. , Holder Graham E.
Published: December 2018

Purpose

To review the clinical characteristics and address the aetiology in a group of patients presenting with unilateral retinal pigmentary changes, best described as unilateral pigmentary retinopathy (UPR).

Methods

The cohort of 42 patients was identified retrospectively from the Moorfields Eye Hospital electrophysiology database. All had undergone full‐field [electroretinography (ERG)] and pattern electroretinography (PERG), with 13 additionally having multifocal ERG (mfERG). The clinical findings, fundus photographs and fundus autofluorescence (AF) images were reviewed.

Results

All index eyes showed ERG evidence of generalized photoreceptor dysfunction with most showing a similar degree of rod and cone involvement. However, although the fellow eyes all had a normal fundus examination, there were bilateral but asymmetrical ERG abnormalities in eight patients and a further four patients had PERG evidence of macular dysfunction in the fellow eye. A relevant medical history or the diagnosis of an ophthalmologic entity that might be related to the unilateral fundus changes was ascertained in 15 cases (~36%) including acute zonal occult outer retinopathy, trauma, systemic malignancy or autoimmune disease, retinal vasculitis, presumed pregnancy‐related choroidal ischaemia and meningitis. Two patients had a family history of retinitis pigmentosa (RP; 4.8%).

Conclusion

The underlying aetiology in most cases of UPR cannot accurately be identified, but an heritable cause is unlikely. Aspects of the history clearly suggest an acquired disorder in some patients. Twenty‐five patients (60%) with nongenetic UPR did not adhere to the pattern of rod greater than cone dysfunction that occurs in RP (rod–cone dystrophy), and the pattern of rod > cone dysfunction seen in true RP is thus not a feature of most patients with UPR.
Novel mutations in mevalonate kinase cause disseminated superficial actinic porokeratosis
Authors: Zhu T. , Tian D. , Zhang L. , Xu X. , Xia K. , Hu Z. , Xiong Z. , Tan J.
Published: December 2018

Background

Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23·2-q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP.

Objectives

To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree.

Methods

The half-life of wild-type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull-down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants.

Results

Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis.

Conclusions

Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.
How Infants' Arousal Influences Their Visual Search
Authors: Kleberg Johan Lundin , del Bianco Teresa , Falck‐Ytter Terje
Published: December 2018

The influence of arousal on visual attention was examined in 6.5‐month‐old infants (N = 42) in the context of a visual search task. Phasic increases in arousal were induced with brief sounds and measured with pupil dilation. Evidence was found for an inverted U‐shaped relation between pupil dilation amplitude and visual orienting, with highest likelihood of a target fixation at intermediate levels of arousal. Effects were similar for facial stimuli and simple objects. Together, these results contribute to our understanding of the relation between arousal and attention in infancy. The study also demonstrates that infants have a bias to orient to human eyes, even when presented in isolation.
Neuromyelitis optica spectrum and myelin oligodendrocyte glycoprotein antibody‐related disseminated encephalomyelitis
Authors: Misu Tatsuro , Fujihara Kazuo
Published: December 2018

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis (MS) has long been debated. With the discovery of an NMO‐specific autoantibody to aquaporin 4 (AQP4), the clinical, radiological, and laboratory findings have clarified the differences between NMO and MS, and NMO spectrum disorders (NMOSD) have been proposed as the unifying term for the entire clinical entity including brain syndromes. Pathological studies in NMO showed loss of immunoreactivity to AQP4 and glial fibrillary acidic protein, but a relative preservation of myelin basic protein, especially at the lesions with perivascular deposition of immunoglobulins and complements. AQP4 antibody‐positive NMOSD is now considered an autoimmune astrocytopathic disease. In addition, the definite diagnosis should be made initially from the therapeutic viewpoint, because there have been several AQP4 antibody‐positive NMOSD cases exacerbated by disease‐modifying drugs for MS. In recent years, the antibody against myelin oligodendrocyte glycoprotein (MOG) has been studied for its association with other types of acute demyelinating diseases, such as acute or multiphasic disseminated encephalomyelitis, optic neuritis, NMOSD and brainstem or cerebral cortical encephalomyelitis. Recent brain biopsied MOG antibody‐positive case reports have suggested the dominance of humoral immunity, but it is not well elucidated whether the cellular immune responses against MOG could develop perivenous inflammatory demyelination like classical acute disseminated encephalomyelitis pathology. In the present review, we focus on two distinct diseases, aquaporin 4 antibody‐related NMOSD and MOG antibody‐related diseases, both of which were recently differentiated from MS by means of the disease‐specific autoantibodies and the distinct pathophysiologies.
LOTUS as a novel biomarker of multiple sclerosis
Authors: Takahashi Keita , Tanaka Fumiaki
Published: December 2018

Multiple sclerosis (MS) is considered to be an autoimmune demyelinating disorder, but recent studies showed that axonal degeneration is also an important pathological feature of MS. Indeed, Nogo receptor‐1 and its ligands have been identified as key molecules for axonal degeneration in various neurological disorders, including MS. Lateral olfactory tract usher substance, an endogenous Nogo receptor‐1 antagonist, promotes axonal growth and regeneration by blocking Nogo receptor‐1 signaling. We found that the lateral olfactory tract usher substance level in cerebrospinal fluid was inversely correlated with MS disease activity. Here, we review the association between the key molecules in axonal degeneration/regeneration and MS, and discuss the potential application of lateral olfactory tract usher substance as a biomarker and therapeutic target of MS.
Prevention and reversal of Type 2 diabetes: highlights from a symposium at the 2019 Diabetes UK Annual Professional Conference
Authors: Taylor R. , Valabhji J. , Aveyard P. , Paul D.
Published: December 2018

Aim

This symposium covers the gamut of Type 2 diabetes prevention, reversing established Type 2 diabetes, population‐level delivery of weight loss programmes and personal insights into achieving and retaining substantial weight loss.

Results

The NHS Diabetes Prevention Programme was launched in 2016 and rates of referral and attendance have both exceeded expectations. By March 2018, mean weight loss for completers (those attending more than 60% of sessions) was 3.2 kg reflecting considerable health benefits. Established Type 2 diabetes is now known to be a reversible condition in the early years, and the underlying mechanism is the removal of the excess fat from within liver and pancreas in these susceptible individuals. The Diabetes Remission Clinical Trial has shown that around half of a primary care population of people with Type 2 diabetes of less than 6 years’ duration can be returned to non‐diabetic blood glucose control which lasts at least 12 months. This raises the question of population‐level intervention to achieve weight loss. The success of some mass weight loss programmes requires to be recognized. Reframing mass provision of weight loss support should be a vital part of our clinical strategy to prevent and treat Type 2 diabetes. However, the current obesogenic environment is a reality in which individuals must live. A personal account of achieving substantial and maintaining substantial weight loss provides an invaluable insight into practical problems encountered. All health professionals dealing with weight control should assimilate and reflect upon this understanding.

Conclusions

Effective prevention and long term reversal of Type 2 diabetes is feasible. The impact upon the individual must be considered during delivery of advice and support.
Pervasive admixture between eucalypt species has consequences for conservation and assisted migration
Authors: von Takach Dukai Brenton , Jack Cameron , Borevitz Justin , Lindenmayer David B. , Banks Sam C.
Published: December 2018

Conservation management often uses information on genetic population structure to assess the importance of local provenancing for ecological restoration and reintroduction programs. For species that do not exhibit complete reproductive isolation, the estimation of population genetic parameters may be influenced by the extent of admixture. Therefore, to avoid perverse outcomes for conservation, genetically informed management strategies must determine whether hybridization between species is relevant, and the extent to which observed population genetic patterns are shaped by interspecific versus intraspecific gene flow. We used genotyping by sequencing to identify over 2,400 informative single nucleotide polymorphisms across 18 populations of Eucalyptus regnans F. Muell., a foundation tree species of montane forests in south‐eastern Australia. We used these data to determine the extent of hybridization with another species, Eucalyptus obliqua L'Hér., and investigate how admixture influences genetic diversity parameters, by estimating metrics of genetic diversity and examining population genetic structure in datasets with and without admixed individuals. We found hybrid individuals at all sites and two highly introgressed populations. Hybrid individuals were not distributed evenly across environmental gradients, with logistic regression identifying hybrids as being associated with temperature. Removal of hybrids resulted in increases in genetic differentiation (FST), expected heterozygosity, observed heterozygosity and the inbreeding coefficient, and different patterns of isolation by distance. After removal of hybrids and introgressed populations, mountain ash showed very little population genetic structure, with a small effect of isolation by distance, and very low global FST(0.03). Our study shows that, in plants, decisions around provenancing of individuals for restoration depend on knowledge of whether hybridization is influencing population genetic structure. For species in which most genetic variation is held within populations, there may be little benefit in planning conservation strategies around environmental adaptation of seed sources. The possibility for adaptive introgression may also be relevant when species regularly hybridize.
Incorporating local adaptation into forecasts of species’ distribution and abundance under climate change
Authors: DeMarche Megan L. , Doak Daniel F. , Morris William F.
Published: December 2018

Populations of many species are genetically adapted to local historical climate conditions. Yet most forecasts of species’ distributions under climate change have ignored local adaptation (LA), which may paint a false picture of how species will respond across their geographic ranges. We review recent studies that have incorporated intraspecific variation, a potential proxy for LA, into distribution forecasts, assess their strengths and weaknesses, and make recommendations for how to improve forecasts in the face of LA. The three methods used so far (species distribution models, response functions, and mechanistic models) reflect a trade‐off between data availability and the ability to rigorously demonstrate LA to climate. We identify key considerations for incorporating LA into distribution forecasts that are currently missing from many published studies, including testing the spatial scale and pattern of LA, the confounding effects of LA to nonclimatic or biotic drivers, and the need to incorporate empirically based dispersal or gene flow processes. We suggest approaches to better evaluate these aspects of LA and their effects on species‐level forecasts. In particular, we highlight demographic and dynamic evolutionary models as promising approaches to better integrate LA into forecasts, and emphasize the importance of independent model validation. Finally, we urge closer examination of how LA will alter the responses of central vs. marginal populations to allow stronger generalizations about changes in distribution and abundance in the face of LA.