bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-frequency tACS has lasting effects on neural synchrony and audiovisual responses
Authors: Bockhorst Tobias , Ahlbeck Joachim , Pieper Florian , Engler Gerhard , Engel Andreas K.
Published: January 2019

BACKGROUND: In cortical networks, synchronized oscillatory activity of neuronal populations enables communication, and its disturbance is related to a range of pathologies. Transcranial alternating current stimulation (tACS) has been explored as a flexible, noninvasive tool for the modulation and restoration of synchronized oscillatory signals. While numerous studies have addressed cognitive or behavioural effects of electrical stimulation, the neural changes underlying the effects of tACS and their persistence after stimulation offset have remained unclear.
OBJECTIVE: Here, we screened for lasting aftereffects of prolonged tACS on intrinsic network activity and audiovisual processing in the anesthetized ferret brain.
METHODS: Electrical stimulation was applied via subcutaneous wire electrodes. Current waveforms were synthesized from two frequencies in the alpha or gamma range, respectively. Flashes and clicks were used for audiovisual stimulation. Electrocorticographic recordings from an extended network including occipital, temporal and parietal cortical areas were obtained before and after tACS.
RESULTS: Changes in local synchrony (continuous and spike-triggered power of LFP), synchrony across recording sites (imaginary coherence) and altered dynamics of sensory response-features (peak-to-peak amplitude, extremum latency) following electrical stimulation consistently point to a synchronizing effect of tACS that can outlast stimulation offset by at least 10 min. Gamma-band tACS proved particularly effective. In line with previous reports on cross-frequency interactions, we observed effects on coherence and power of baseline activity at frequencies other than the ones targeted by tACS. These cross-frequency interactions appeared to underlie the strengthening and stabilizing effect on audiovisual responses.
CONCLUSION: We demonstrate aftereffects of tACS on synchrony and stimulus processing in an extended cortical network, measured intracranially in a setting that resembles tACS stimulation in humans. The data provide direct evidence for the efficacy of tACS as a tool for sustained modulation of cortical network dynamics.
Aberrations in Notch-Hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion
Authors: Chang Wai Hoong , Lai Alvina G
Published: January 2019

Background: Cancer stem cells (CSCs) have innate abilities to resist even the harshest of therapies. To eradicate CSCs, parallels can be drawn from signalling modules that orchestrate pluripotency. Notch-Hedgehog hyperactivation are seen in CSCs, yet, not much is known about their conserved roles in tumour progression across cancers.
Methods: Employing a comparative approach involving 21 cancers, we uncovered clinically-relevant, pan-cancer drivers of Notch and Hedgehog. GISTIC datasets were used to evaluate copy number alterations. Receiver operating characteristic and Cox regression were employed for survival analyses.
Results: We identified a Notch-Hedgehog signature of 13 genes exhibiting high frequencies of somatic amplifications leading to transcript overexpression. The signature successfully predicted patients at risk of death in five cancers(n=2,278): glioma(P<0.0001), clear cell renal cell(P=0.0022), papillary renal cell(P=0.00099), liver(P=0.014) and stomach(P=0.011). The signature was independent of other clinicopathological parameters and offered additional resolution to stratify similarly-staged tumours. High-risk patients exhibited features of stemness and had more hypoxic tumours, suggesting that hypoxia may influence CSC behaviour. Notch-Hedgehog+ CSCs had an immune privileged phenotype associated with increased regulatory T cell function.
Conclusion: This study will set the stage for exploring adjuvant therapy targeting the Notch-Hedgehog axis to help optimise therapeutic regimes leading to successful CSC elimination.
Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides
Authors: Chang Zanetta , Billmyre R. Blake , Lee Soo Chan , Heitman Joseph
Published: January 2019

Mucormycosis - an emergent, deadly fungal infection - is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Epimutations silence the drug target gene and are selected by drug exposure; the target gene is re-expressed and sensitivity is restored following passage without drug. This silencing process involves generation of small RNA (sRNA) against the target gene via core RNAi pathway proteins. To further elucidate the role of epimutation in the broad antifungal resistance of Mucor, epimutants were isolated that confer resistance to another antifungal agent, 5-fluoroorotic acid (5-FOA). We identified epimutant strains that exhibit resistance to 5-FOA without mutations in PyrF or PyrG, enzymes which convert 5-FOA into the active toxic form. Using sRNA hybridization as well as sRNA library analysis, we demonstrate that these epimutants harbor sRNA against either pyrF or pyrG, and further show that this sRNA is lost after reversion to drug sensitivity. We conclude that epimutation is a mechanism capable of targeting multiple genes, enabling Mucor to develop resistance to a variety of antifungal agents. Elucidation of the role of RNAi in epimutation affords a fuller understanding of mucormycosis. Furthermore, it improves our understanding of fungal pathogenesis and adaptation to stresses, including the evolution of drug resistance.
Fate plasticity and reprogramming in genetically distinct populations of Danio leucophores
Authors: Lewis Victor , Saunders Lauren , Larson Tracy A , Bain Emily , Sturiale Samantha , Gur Dvir , Chowdhury Sarwat , Flynn Jessica , Allen Michael , Deheyn Dimitri , Lee Jennifer , Simon Julian , Lippincott-Schwartz Jennifer , Raible David , Parichy David
Published: January 2019

Understanding genetic and cellular bases of adult form remains a fundamental goal at the intersection of developmental and evolutionary biology. The skin pigment cells of vertebrates, derived from embryonic neural crest, are a useful system for elucidating mechanisms of fate specification, pattern formation, and how particular phenotypes impact organismal behavior and ecology. In a survey of Danio fishes, including zebrafish Danio rerio, we identified two populations of white pigment cells--leucophores--one of which arises by transdifferentiation of adult melanophores and another that develops from a yellow/orange xanthophore-like progenitor. Single-cell transcriptomic, mutational, chemical and ultrastructural analyses of zebrafish leucophores revealed cell-type specific chemical compositions, organelle configurations and genetic requirements. At the organismal level, we identified distinct physiological responses of leucophores during environmental background matching and we show that leucophore complement influences behavior. Together, our studies revealed new, independently arisen pigment cell types and mechanisms of fate acquisition in zebrafish, and illustrate how concerted analyses across hierarchical levels can provide insights into phenotypes and their evolution.
Krüppel-like factor gene function in the ctenophore Mnemiopsis leidyi assessed by CRISPR/Cas9-mediated genome editing
Authors: Presnell Jason S , Browne William E
Published: January 2019

The Krüppel-like factor (Klf) gene family encodes for transcription factors that play an important role in the regulation of stem cell proliferation, cell differentiation, and development in bilaterians. While Klf genes have been shown to functionally specify various cell types in non-bilaterian animals, their role in early diverging animal lineages has not been assessed. Thus, the ancestral activity of these transcription factors in animal development is not well understood. The ctenophore Mnemiopsis leidyi has emerged as an important non-bilaterian model system for understanding early animal evolution. Here we characterize the expression and functional role of Klf genes during M. leidyi embryogenesis. Zygotic Klf gene function was assessed with both CRISPR/Cas9-mediated genome editing and splice-blocking morpholino oligonucleotide knockdown approaches. Abrogation of zygotic Klf expression during M. leidyi embryogenesis results in abnormal development of several organs including the pharynx, tentacle bulbs, and apical organ. Our data suggest an ancient role for Klf genes in regulating endodermal patterning, possibly through regulation of cell proliferation.

Summary Statement

Using CRISPR/Cas9 genome editing and morpholino oligonucleotide knockdown, this study shows that tissues derived from the endoderm are dependent upon Klf5 ortholog expression for proper development and patterning in the ctenophore Mnemiopsis leidyi.
A new ternary compound with the BGa8Ir4 structure type in the Al–Au–Ir system
Authors: Kadok Joris , de Weerd Marie-Cécile , Boulet Pascal , Fournée Vincent , Ledieu Julian
Published: January 2019

Following the recent determination of the Al3AuIr structure, a new ternary phase has been identified in the Al–Au–Ir phase diagram. It has a chemical composition Al9(Au;Ir)4 with an apparently low gold content. Its crystal structure has been determined with single-crystal X-ray diffraction. The new compound crystallizes in the tetragonal crystal system and has been successfully solved in space group I41/acd (Pearson symbol tI104) with lattice parameters a = 8.6339 (2) and c = 21.8874 (7) Å. Atomic environments are described as well as similarities with the BGa8Ir4 compound.
Business incubator training management model to increase graduate competency
Authors: Sudana I Made , Apriyani Delta , Supraptono Eko , Kamis Arasinah
Published: January 2019

Purpose

The purpose of this paper is to produce a business incubator training model for students to form graduates in order to have competence in the field of entrepreneurship in an effort to reduce high unemployment.

Design/methodology/approach

The method used in this study was research and development (R&D) that consisted of the following five stages: first, planning based on the result of initial observation in the field, second, development of training model, third, validity test model, fourth, limited test and fifth, final model determination. This research used and involved 12 beauty successful beauty salon entrepreneurs as validator models of business incubator training management.

Findings

The test results show that the training model developed is effective in forming entrepreneurship competence of graduates, so it is feasible to be applied in Beauty Education Study Program, Engineering Faculty of Universitas Negeri Semarang.

Practical implications

The resulted model can be used as a learning model that can develop the skill of entrepreneurship level for students.

Originality/value

This study provides contribution to the unemployment level decrease and employment acceleration.
Development of a benchmarking model for BIM implementation in developing countries
Authors: Olawumi Timothy O. , Chan Daniel W.M.
Published: January 2019

Purpose

The purpose of this paper is to explore building information modeling (BIM) implementation and practices in developed economies by developing a benchmarking model that will enhance BIM adoption and implementation in developing countries.

Design/methodology/approach

The research design adopted a qualitative approach which includes the desktop review of the extant literature as well as case study reviews of ten BIM projects using an explanatory case study technique to form the foundation upon which the study proposed the model. The moving basis heuristics technique was adopted to develop the scoring system.

Findings

The BIM benchmarking model and assessment template were developed which consisted of three-level concepts modeled to aid project organizations and project team in developing countries to assess and score the level of improvement and implementation of BIM in a project. A desktop review of BIM projects in developed countries demonstrated the significant improvements and benefits possible through the implementation of the established BIM benchmarking model.

Practical implications

The assessment template in conjunction with the benchmarking model is useful for a comparative evaluation of similar BIM projects and benchmarking purposes. The study also discussed how current findings extends and contradicts previous findings.

Originality/value

The findings have provided policymakers, construction stakeholders and professional bodies in the construction industry in developing countries with valuable insights and counter-intuitive perspective that could facilitate the uptake of BIM in construction projects.
Supply chain redesign for lead-time reduction through Kraljic purchasing portfolio and AHP integration
Authors: Bianchini Augusto , Benci Andrea , Pellegrini Marco , Rossi Jessica
Published: January 2019

Purpose

The purpose of this paper is to provide a flexible and extensible model for the classification of suppliers, within the purchasing guidelines and market trends of an Italian small company, leader in the production of street lamps. The model is applied to identify critical supply chains with the final objective of lead-time reduction.

Design/methodology/approach

The model is obtained by the application of the purchasing portfolio analysis through the construction of Kraljic matrix. Profit impact and supply risk criteria are selected according to the main company requirements, and then prioritized by the analytical hierarchy process (AHP). Finally, supply chain lead-times are analyzed with Gantt diagrams.

Findings

The application of the model allows the determination of company criticalities in terms of high lead-times and of the involved suppliers. The analysis of critical suppliers positioning in the Kraljic matrix allows the definition of some possible strategies to implement for lead-time reduction.

Research limitations/implications

Purchasing portfolio analysis and Kraljic matrix are practical instruments to quickly frame company purchasing situation, but their application is not simple due to the numerous and different factors involved, especially in small and medium enterprises (SMEs), where resource are scarce and several constraints limit operations. The objective of the research is the development of a practical tool for strategic purchasing, simple and robust to be implemented in SMEs, with limited resources and access to quantitative supplier data.

Originality/value

Evaluation criteria definition is one of the most difficult phases, such as their univocal and quantitative comparison. The problem of selecting and prioritizing both quantitative and qualitative criteria for suppliers classification is overcome with the combined application of Kraljic matrix and AHP. The newly integration of the two methodologies allows the realization of a reliable and robust model for suppliers classification, which can be easily adapted to company business strategy changes.
The limits of consequential reasoning in shared value creation
Authors: Lee Jooho
Published: January 2019

Purpose

This paper aims to move beyond the limits of creating shared value (CSV) by presenting a norms-driven framework for creating shared value.

Design/methodology/approach

This paper combines insights from organizational studies and philosophy to critique CSV and to articulate an alternative model for integrating the pursuit of profit with social needs and demands.

Findings

CSV poses significant challenges for managers due to the problem of bounded rationality. Rather than merely engaging in a logic of consequence, this paper argues that managers should integrate norms-based reasoning within the cognitive process of strategic management.

Originality/value

This paper critiques an existing framework for creating shared value and proposes a new framework.
Embedding employability within higher education for the profession of policing
Authors: Pepper Ian , McGrath Ruth
Published: January 2019

Purpose

The purpose of this paper is to evaluate the impact of an employability module, the College of Policing Certificate in Knowledge of Policing (CKP), on students’ career aspirations, their confidence and wish to join the police along with the appropriateness of the module. This will inform the implementation of employability as part of the College of Policing-managed Police Education Qualifications Framework (PEQF).

Design/methodology/approach

A three-year longitudinal research study used mixed methods across four points in time to evaluate the impact on students studying the employability module.

Findings

The research suggests that the employability-focussed CKP was useful as an introduction to policing, it developed interest in the police and enhanced the confidence of learners applying to join. Lessons learnt from the CKP should be considered during the implementation of the PEQF.

Research limitations/implications

The ability to generalise findings across different groups is limited as other influences may impact on a learner’s confidence and employability. However, the implications for the PEQF curriculum are worthy of consideration.

Practical implications

As the police service moves towards standardised higher educational provision and evolution of policing as a profession, lessons can be learnt from the CKP with regards to the future employability of graduates.

Originality/value

Enhancing the employability evidence base, focussing on policing, the research identified aspects which may impact on graduates completing a degree mapped to the PEQF. The research is therefore of value to higher education and the professional body for policing.
Economic, social and cultural rights of women
Authors: Arif Sardar M.A. Waqar Khan
Published: January 2019

Purpose

The purpose of this paper is to highlight the legal framework and challenges to economic, social and cultural (ESC) rights of women.

Design/methodology/approach

This paper focuses on ESC rights of women. ESC rights are recognized under primary instrument International Covenant on Economic, Social and Cultural Rights (ICESCR), which is adopted by the United Nations (UN) in 1966. States have obligations to respect, protect and fulfil ESC rights. This paper aims to address ESC rights of women in particular. It analyzes the international legal framework including provisions of UN Charter, the Universal Declaration of Human Rights (UDHR) and ICESCR and its optional protocol. It also analyzes provisions of Women’s Convention and identifies its linkage to ICESCR.

Findings

ESC rights are not justiciable and growing debate over justiciability is important for consideration. Also, there exist certain challenges for the progressive realization of ESC rights which need to be addressed by analyzing provisions of the existing legal framework and Maastricht Guidelines. The argument developed throughout the paper is that women’s ESC rights may be protected at all levels by the progressive realization of these rights. The issue of justiciability may also be resolved to protect the basic needs and interests of women that leads to their empowerment.

Originality/value

The work is original and not published by any other journal so far.
Determinants of tax stamp evasion in rural districts in Ghana
Authors: Amponsah Stephen , Isshaq Zangina , Agyapong Daniel
Published: January 2019

Purpose

The purpose of this study is to examine tax stamp evasion at Twifu Atti-Morkwa and Hemang Lower Denkyira districts in the central region of Ghana.

Design/methodology/approach

A cross-sectional survey design was adopted to sample 305 micro-taxpayers through the use of multi-stage sampling technique. Primary data were collected from the micro-taxpayers using structured interview. Binary and multinomial logit regression models were used to regress the tax stamp evasion on economic and non-economic factors.

Findings

The study found that the likelihood of micro taxpayers to evade tax stamp is predicted by age, application of sanctions, guilt feeling, transportation cost to tax office and rate of tax audit. Thus, the study found partial support for expected utility, planned behaviour and attributory theories in explaining tax evasion behaviour of micro-taxpayers.

Practical/implication

There are several measures of addressing tax evasion behaviour of micro taxpayers. Evasion behaviour can be deterred by enforcement strategies such as application of sanctions and regular tax audit, establishment of more tax offices in the districts and writing normative messages on the faces of tax stamp stickers.

Originality/value

This study helps explains the tax evasion behaviour of micro-taxpayers of a developing economy like Ghana using a special type of tax design meant to capture such taxpayers in the tax bracket. To the best of our knowledge, the study is unique in terms of the means of measuring tax evasion and the methodologies used.
The effect of FDI on domestic investment and economic growth case of three Maghreb countries
Authors: Ali Walid , Mna Ali
Published: January 2019

Purpose

The purpose of this study is to show how foreign direct investment (FDI) affects domestic investment and economic growth. This study empirically examines this question in the case of three developing countries (Tunisia, Algeria and Morocco).

Design/methodology/approach

Using the GMM estimator technique, the authors constructed a system with simultaneous equations by three endogenous variables: economic growth (GDP), FDI and domestic investment (DI).

Findings

The study was a nuance, its results, at the role of investment–growth relationship, are of paramount importance though subtle and slightly different.

Originality/value

The authors used data from international institutions such as the IMF, UNCTAD, OECD and the World Bank for macroeconomic aggregates. However, the interest rate variables are derived from the central banks of the three countries in the sample. The analysis covers the period from 1980 to 2014.
How does the real earnings management affect firms innovative? Evidence from US firms
Authors: Chouaibi Jamel , Zouari Ghazi , Khlifi Sawssen
Published: January 2019

Purpose

The purpose of this paper is to examine the effect of R&D intensity on the real earnings management index.

Design/methodology/approach

The authors proceed with dividing the full sample into two sub-samples, in accordance with the R&D associated intensity median. The final test sample proves to involve 73 firms along with 949 relating observations, while the control sample appears to enclose 65 firms and 845 relevant observations for the period 2000-2012.

Findings

The main finding of this study is the great influence of R&D intensity on the real earnings management index on the test sample. Accordingly, the proposed hypothesis stipulating that the innovative firms engage in upward real earnings management turns out to be strongly supported.

Research limitations/implications

The study was conducted using robust methods to test the effect of R&D intensity on the real earnings management index. The generalized least squares method was used to fit panel data and overcome heteroscedasticity and autocorrelation problems. The aim of the study was to prove the great effect of R&D intensity on the real earnings management index. As this study was based on data from American companies, the results cannot be generalized to all contexts.

Originality/value

This paper differs from previous work and tests the effect of innovative firms, the market-to-book ratio on real earnings management. The findings of this study will enrich the literature on real earnings management by suggesting R&D intensity that can significantly enhance the real earnings management index. Therefore, these findings will be helpful to investors, managers and regulators because they have implications for the interactive decision-making process.
The investment law development to increase investment in Indonesia
Authors: Suradiyanto Suradiyanto
Published: January 2019

Purpose

The law development, especially in the field of investment, is not only directed to achieve the vision of Indonesia 2030, but it is directed to make Indonesia a great nation, protect the potential and plurality of Indonesia and realize the welfare of the nation, both economically independent and having qualified human resources. Based on the description, the purpose of this paper is to examine and find forms of refinement in the investment law development of Indonesia in accordance with the global order.

Design/method

This paper is qualitative research. This paper examines and finds forms of refinement in the investment law development of Indonesia in accordance with the global order.

Findings

The refinement form of investment law development in Indonesia in accordance with the global order begins with Law Number 1 of 1967 on Foreign Investment (PMA) and Law Number 6 of 1968 concerning Domestic Investment (PMDN), which is then followed by the issuance of Presidential Decree Number 29 of 2004 concerning the Implementation of Investment in Foreign Capital Investment (PMA) and Domestic Investment (PMDN) through One Stop Service System. The reconstruction form of the capital investment law is by the issuance of Law Number 25 of 2007 regarding Investment which regulates the domestic investment and foreign investment. The authorized official to coordinate the implementation of investment in Indonesia is the Investment Coordinating Board (BKPM). The consideration of BKPM appointment as the only government agency that handles investment activities of PMA and PMDN is to increase the effectiveness in attracting investors to invest in Indonesia. Therefore, by one stop service, it is expected that the service to the investors will be faster than the previous implementation. One Stop Service System means that the implementation of investment consists of policies and planning of investment development, promotion and investment cooperation, approval services, licensing and investment facilities, control of investment implementation and management of investment information system. Approval services, licensing and investment facilities on PMA and PMDN shall be implemented by BKPM, based on the delegation of authority from the Minister/Head of Non-Department Institution which handle the relevant investment business fields through one stop service system.

Originality/value

This paper only focuses on the investment law development in Indonesia that has never been done before (originality).
Silkworm as an experimental animal for research on fungal infections
Authors: Matsumoto Yasuhiko , Sekimizu Kazuhisa
Published: January 2019

Silkworm, Bombyx mori, has various advantages as an experimental animal, such as the low cost for rearing and fewer ethical problems. Models utilizing silkworms of infection with pathogenic bacteria have been established for identification of genes encoding virulence factors by large‐scale in vivo screening. In this review, we describe recent progress in the study of silkworm infection models for elucidating the mechanisms of fungi infection. Silkworm infection models have been established for Candida albicans, Candida tropicalis, Candida glabrata and Cryptococcus neoformans, which are yeast type fungi, and Aspergillus fumigatus, Arthroderma vanbreuseghemii, Arthroderma benhamiae, Microsporum canis, Trichophyton rubrum, and Rhizopus oryzae, which are filamentous fungi. Novel genes encoding virulence factors in C. albicans and C. glabrata have been identified by using the silkworm infection models. We here outline the benefits of using silkworm infection models and a strategy for identifying the genes responsible for pathogenicity of microorganisms such as fungi. © 2019 The Authors. Microbiology and Immunology Published by The Societies and John Wiley & Sons Australia, Ltd.
Coral reef ecology in the Anthropocene
Authors: Williams Gareth J. , Graham Nicholas A. J. , Jouffray Jean‐Baptiste , Norström Albert V. , Nyström Magnus , Gove Jamison M. , Heenan Adel , Wedding Lisa M.
Published: January 2019

We are in the Anthropocene—an epoch where humans are the dominant force of planetary change. Ecosystems increasingly reflect rapid human‐induced, socioeconomic and cultural selection rather than being a product of their surrounding natural biophysical setting. This poses the intriguing question: To what extent do existing ecological paradigms capture and explain the current ecological patterns and processes we observe?

We argue that, although biophysical drivers still influence ecosystem structure and function at particular scales, their ability to offer predictive capacity over coupled social–ecological systems is increasingly compromised as we move further into the Anthropocene.

Traditionally, the dynamics of coral reefs have been studied in response to their proximate drivers of change rather than their underlying socioeconomic and cultural drivers. We hypothesise this is limiting our ability to accurately predict spatial and temporal changes in coral reef ecosystem structure and function.

We propose “social–ecological macroecology” as a novel approach within the field of coral reef ecology to a) identify the interactive effects of biophysical and socioeconomic and cultural drivers of coral reef ecosystems across spatial and temporal scales; b) test the robustness of existing coral reef paradigms; c) explore whether existing paradigms can be adapted to capture the dynamics of contemporary coral reefs; and d) if they cannot, develop novel coral reef social–ecological paradigms, where human dynamics are part of the paradigms rather than the drivers of them.

Human socioeconomic and cultural processes must become embedded in coral reef ecological theory and practice as much as biophysical processes are today if we are to predict and manage these systems successfully in this era of rapid change. This necessary shift in our approach to coral reef ecology will be challenging and will require truly interdisciplinary collaborations between the natural and social sciences.

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Converting the DriveSafe subtest of DriveSafe DriveAware for touchscreen administration
Authors: Cheal Beth , Bundy Anita , Patomella Ann‐Helen , Scanlan Justin Newton , Wilson Christopher
Published: January 2019

Background

DriveSafe measures awareness of the driving environment. It is one subtest of DriveSafe DriveAware, a cognitive fitness‐to‐drive screening instrument. We converted DriveSafe to a touchscreen format for ease of administration; this necessitated the development of an automatic data collection and scoring system to reflect the decision that would otherwise have been made by an expert rater. We applied a structured process to determine what constituted ‘correct’ scores. We then examined the resulting scoring parameters to determine if these discriminated at‐risk drivers from a comparison sample.

Methods

Thirty at‐risk older drivers and 30 younger drivers took touchscreen DriveSafe. Following presentation of images containing between one and four objects/hazards for 4 seconds, participants indicated their recall of object/hazard characteristics (type, location and direction of movement) by touching the screen. We analysed responses via descriptive statistics to compare spread, accuracy and consistency; and via a Fisher's exact test to determine whether the set scoring parameters could discriminate between at‐risk and comparison drivers.

Results

Fisher's exact test results indicated 24 of 28 location zones and 18 of 28 direction ranges discriminated at‐risk drivers from the comparison group (P < 0.05). Frequency of missed or incorrectly identified hazards was much higher for the at‐risk group for all variables. At‐risk drivers missed or misidentified significantly (P < 0.00) more object types (34%), directions (47%), and locations (36%) than the comparison group (≤4% for each variable). At‐risk drivers entered 31 additional responses for objects/hazards not displayed; the comparison group entered no additional responses.

Conclusion

The automatic variable data collection and scoring system reflected decisions that would have been made by an expert rater. This systematic process provided automated scoring decisions that enabled us to discriminate at‐risk drivers from a comparison group. Psychometric evaluation of data gathered with touchscreen DriveSafe is required prior to use in clinical practice.
Managing food insecurity through informal networks of care: an ethnography of youth practices in the North of England
Authors: Laverty Louise
Published: January 2019

Food insecurity in the UK is a pressing concern that is associated with poor health outcomes. Research to date has focused on the challenges for adults in providing food for families. However, there is little evidence showing how children and young people experience food insecurity, particularly outside of the home and school. This paper, drawing on 14 months of ethnography in a youth club in the North of England, explores how young people manage food insecurity. In this youth club, the circulation of takeaway food is part of an informal network where boys purchase, share and receive food. This practice allows the boys to participate meaningfully within their peer groups whilst also providing stable access to food. This peer practice, however, was not available to everyone. This was a gendered practice that for the girls held little benefit due to their concerns about eating and pressure to provide for others. Instead, some girls depend on romantic relationships for food provision that is equated with affection and care. The findings will be discussed through a ‘materialities of care’ perspective to explore the complex ways in which food as a practice of care is part of everyday routines embedded within local places.
County‐level access to opioid use disorder medications in medicare Part D (2010‐2015)
Authors: Abraham Amanda J. , Adams Grace Bagwell , Bradford Ashley C. , Bradford William D.
Published: January 2019

Objective

To identify geographic disparities in access to opioid use disorder (OUD) treatment medications and county demographic and economic characteristics associated with access to buprenorphine and oral naltrexone prescribers in Medicare Part D.

Data Sources/Study Setting

We utilized data from the Medicare Part D Prescription Drug Event Standard Analytic File (2010‐2015).

Study Design/Data Collection

We used logistic regression to examine county‐level access to OUD medication prescribers.

Principal Findings

There was a 5.6 percentage point increase in counties with access to an OUD prescriber over the study period. However, in 2015, 60 percent of US counties lacked access to a Medicare Part D buprenorphine prescriber and over 75 percent lacked access to an oral naltrexone prescriber. Increased access to OUD prescribers was largely concentrated in urban counties. Results of logistic regression indicate regional differences and potential racial disparities in access to OUD prescribers.

Conclusions

To improve access to buprenorphine and naltrexone treatment for Medicare Part D enrollees, CMS may consider implementing educational and training initiatives focused on OUD treatment, offering training to obtain a buprenorphine waiver at no cost to providers, and sending targeted information to providers in low OUD treatment capacity areas.
Iguratimod ameliorates bleomycin‐induced alveolar inflammation and pulmonary fibrosis in mice by suppressing expression of matrix metalloproteinase‐9
Authors: Zhao Like , Mu Bingyao , Zhou Rongwei , Cheng Yongjing , Huang Cibo
Published: January 2019

Aim

To investigate the potential therapeutic efficacy of iguratimod (IGU) on bleomycin (BLM)‐induced pulmonary fibrosis in mice.

Methods

A total of 75 C57BL/6 mice were randomly and evenly divided into control group, BLM (5 mg/kg) group, BLM + IGU (90 mg/kg) group, BLM + methylprednisolone (MP, 10 mg/kg) group and BLM + pirfenidone (PF, 100 mg/kg) group. The mice were sacrificed on day 7, 14 and 28. The lung tissue was examined by hematoxylin and eosin staining and Masson staining to evaluate the degree of alveolitis and fibrosis, and serum cytokines were measured.

Results

Histopathological results showed that IGU attenuated BLM‐induced alveolar inflammation and decreased collagen deposition in lung tissue from day 7 till day 28. Both the pathological alveolitis and fibrosis scores in the drug‐treated groups (IGU group, MP group and PF group) were decreased dramatically compared with the BLM group on day 7, 14 and 28 (P < 0.05). There were no statistical significances among these three groups. Cytokine profile showed that IGU decreased the level of tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1, IL‐6 and matrix metalloproteinase (MMP)‐9 which were up‐regulated by BLM on day 7, 14 and 28 (P < 0.05). Furthermore, there is a strong correlation between the severity of pulmonary fibrosis and serum MMP‐9 levels.

Conclusion

IGU can decrease BLM‐induced pulmonary fibrosis, and the anti‐fibrotic effect of IGU is mediated partly via inhibition of MMP‐9, which suggests that IGU could potentially be an effective therapeutic strategy for pulmonary fibrosis.
Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways
Authors: Cao Pikun , Liu Bin , Du Feng , Li Dong , Wang Yongzheng , Yan Xiaoyan , Li Xiao , Li Yuliang
Published: January 2019

Background

Scutellarin (SCU), a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.‐Mazz., increases autophagy and apoptosis in the adenocarcinoma A549 cell line, which is resistant to cisplatin. However, whether SCU alone has antitumor activity against non‐small cell lung cancer (NSCLC) is unknown.

Methods

Cell Counting Kit‐8, flow cytometry, colony formation, Hoechst 33258 staining, and Western blot analyses were used to examine the proliferation and apoptosis of A549 cells treated with SCU and the possible molecular mechanisms.

Results

The cell viability assay indicated that SCU markedly suppressed the proliferation of A549 cells in concentration and time‐dependent manners. SCU caused significant G0/G1 phase arrest and apoptosis, as evidenced by flow cytometric analyses, Hoechst 33258 staining, and Western blot analyses of cyclin D1, cyclin E, BCL‐2, cleaved‐caspase‐3, and BAX. Furthermore, SCU treatment reduced the level of pan‐AKT, phosphorylated (p)‐mTOR, mTOR, BCL‐XL, STAT3, and p‐STAT3, and increased the level of 4EBP1.

Conclusions

SCU can suppress proliferation and promote apoptosis in A549 cells through AKT/mTOR/4EBP1 and STAT3 pathways. This suggests that SCU may be developed into a promising antitumor agent for treating NSCLC.
Management of anlotinib‐related adverse events in patients with advanced non‐small cell lung cancer: Experiences in ALTER‐0303
Authors: Si Xiaoyan , Zhang Li , Wang Hanping , Zhang Xiaotong , Wang Mengzhao , Han Baohui , Li Kai , Wang Qiming , Shi Jianhua , Wang Zhehai , Cheng Ying , Shi Yuankai , Chen Weiqiang , Wang Xiuwen , Luo Yi , Nan Kejun , Jin Faguang
Published: January 2019

Background

Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐Kit). In the phase III ALTER‐0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non‐small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial.

Methods

Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification.

Results

Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand‐foot syndrome, and 38 (12.9%) patients received anti‐diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively.

Conclusion

Anlotinb‐related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification.
Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation
Authors: Dai Yun‐Jian , Wu Deng‐Chang , Feng Bo , Chen Bin , Tang Yang‐Shun , Jin Miao‐Miao , Zhao Hua‐Wei , Dai Hai‐Bin , Wang Yi , Chen Zhong
Published: January 2019

Aims

Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early‐life FSs could transmit across generations or not.

Methods

The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects.

Results

Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs.

Conclusions

Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases.
NT‐4/5 antagonizes the BDNF modulation of corticostriatal transmission: Role of the TrkB.T1 receptor
Authors: Torres‐Cruz Francisco M. , César Vivar‐Cortés Israel , Moran Isaac , Mendoza Ernesto , Gómez‐Pineda Victor , García‐Sierra Francisco , Hernández‐Echeagaray Elizabeth
Published: January 2019

Neurotrophins are related to survival, growth, differentiation and neurotrophic maintenance as well as modulation of synaptic transmission in different regions of the nervous system. BDNF effects have been studied in the striatum due to the trophic role of BDNF in medium spiny neurons; however, less is known about the effects of NT‐4/5, which is also present in the striatum and activates the TrkB receptor along with BDNF. If both neurotrophins are present in the striatum, the following question arises: What role do they play in striatal physiology? Thus, the aim of this study was to determine the physiological effect of the sequential application and coexistence of BDNF and NT‐4/5 on the modulation of corticostriatal synapses. Our data demonstrated that neurotrophins exhibit differential effects depending on exposure order. BDNF did not modify NT‐4/5 effect; however, NT‐4/5 inhibited the effects of BDNF. Experiments carried out in COS‐7 cells to understand the mechanisms of this antagonism, indicated that NT‐4/5 exerts its inhibitory effect on BDNF by upregulating the TrkB.T1 and downregulating the TrkB‐FL isoforms of the TrkB receptor.
Predictive validity of objective measures of physical fitness for the new onset of mental disorders in adolescents and young adults
Authors: Tacchi Mary Jane , Heggelund Jorn , Scott Jan
Published: January 2019

Aim

To systematically review evidence that objectively assessed level of physical fitness is associated with future risk of adverse mental health outcomes during the peak age range for onset of adult mental disorders.

Methods

Searches of Electronic databases (EBSCOhost, SPORTDISCUS, EMBASE, MedLINE, Cochrane database, CINAHL, PsychInfo, and Dissertation Abstracts), supplemented by hand searches of journals, conference proceedings and citations. Random‐effects meta‐analysis models were used to pool the intervention effects.

Results

Eight studies of adolescents and young adults were included in the qualitative review and six studies derived from four independent cohorts were included in the statistical analyses. Most publications reported on large samples (including >1 million), but male conscripts were over‐represented in the study cohorts; quality of included studies was modest, and heterogeneity was significant. Meta‐analytic estimates were conducted for different adverse mental health outcomes, but all showed an inverse association between fitness and incidence of mental disorders or suicidality. Overall, higher level of physical fitness was associated with lower rates of onset of mental health problems (odds ratio: 0.59; 95% confidence intervals: 0.54, 0.65).

Conclusions

All eligible studies were undertaken since 2010, suggesting this is an emerging but unfinished field of research. The study design and methodological limitations indicate that the reported results should be treated with caution. However, if the meta‐analytic findings are reliably replicated for new cohorts of males and females, they have implications for research into the prevention of non‐communicable diseases, as our review suggests that interventions should target physical and mental health in equal measure.