bluuebunny/crossref_metadata_2025 huggingface dataset:
Networked interdependencies and interaction in a biotechnology research project
Authors: Janusz Artur , Bednarek Agata , Komarowski Leszek , Boniecki Pawel , Engelseth Per
Published: November 2018

Purpose

The purpose of this paper is to reveal the interdependencies involved and how interaction takes place in the context of a project organization as a network of academic and business actors.

Design/methodology/approach

This study focuses on relationships between business and academia and applies a single case research strategy. Data are collected through a series of theoretically sampled in-depth interviews including company observations. The single case study provides a rich narrative of the network structure and processes involved in establishing, implementing and completing a research project in Poland. The Industrial Marketing and Purchasing Group network approach focusing on resource combinations that emerge in a network structure characterized by interdependency and integration is applied to analyze interaction in this project-organized network.

Findings

Change in interdependencies, interaction and integration are analyzed individually, and in conclusion in relation to each other. While supply chain management literature postulates that integration is a management goal, a driver of successful business, this study points out that integration is an outcome of interaction in a context of changing interdependencies. This means that managerial focus should rather be driven to understanding the nature of network interdependencies, their path of change and how interaction is carried out in this emergent context.

Originality/value

The study aims to help better understand the potential for research project cooperation by explaining how businesses and research units can cooperate through an understanding that integration is a complex phenomenon, focusing on how management may better support services production through careful consideration of that integration is developed through considerations of interdependencies as context of interaction in the varied business cultures a project network comprises. Project management is more a learning process than a planning process.
Elder mistreatment in South Asian communities: a review of the literature
Authors: Talpur Ashfaque Ahmed , Ryan Tony , Ali Parveen , Hinchliff Sharron
Published: November 2018

Purpose

The purpose of this paper is to perform a review of the literature of empirical studies on elder mistreatment (EM) in South Asians, and to discuss key implications for policy, practice and research.

Design/methodology/approach

For this review, multiple electronic databases in the international health and social science were searched and supplemented by grey literature and cross-references. Quality of papers was assessed by two authors against the standard checklists.

Findings

In total, 16 studies met the inclusion criteria of this review, of which 11 were cross-sectional design, and only six of them used standard instruments to measure EM. The prevalence estimates of overall EM retrieved from general population-based studies ranged from 9.3 per cent in India to 49.1 per cent in Nepal. Age, gender, residential settings, socioeconomic status, health, education, and social structures and processes were key risk factors for EM in South Asian communities. Reporting and action taking were culturally rooted.

Originality/value

While the review is not systematic, there are limitations associated with the paper in covering the diverse range of databases and studies. However, this review provides a valuable synthesis of the empirical papers on the incidence, culturally specific risk factors and reporting trends of EM in South Asians. Additionally, the review presents the papers evaluated for a quality to ensure the validity of empirical data. Finally, the review includes several implications for policy, practice and future research on EM which may ultimately contribute in improving the health and wellbeing of elder South Asians.
Research on the relationship of the weaker enterprises post-merger brand strategy and consumers’ purchase intention
Authors: Yao Peng , Wang Xinxin
Published: November 2018

Purpose

Nowadays, many weak brands have acquired strong international brands to accelerate their internationalization. However, “the weakers acquire the strongers” model of M&A leads to many consumers’ loss. The purpose of this paper is to explore the relationships between the brand strategy after the M&A, brand authenticity and consumer purchase intention through two experiments.

Design/methodology/approach

Building on an extensive literature review, the authors identify four hypotheses. Hypotheses were tested on data collected across 190 Chinese consumers.

Findings

The results show that the decline of consumer purchase intention was mainly caused by the falling consumer assesses on brand authenticity; the different post-merger brand strategies have significant difference on brand authenticity and consumer purchase intention, and self-brand connection played a moderate role between brand authenticity and consumer purchase intention.

Originality/value

The research reveals the reasons for consumer loss after mergers and acquisitions and provides empirical insights into how post-merger brand strategies can be manifested to convey brand authenticity as well as to build consumers’ purchase intention. In addition, the findings confirm the role of self-brand connection.
Effects of brand alliance on brand equity
Authors: Ma Baolong , Cheng Feiyan , Bu Jingjing , Jiang Jiefan
Published: November 2018

Purpose

Although brand alliance has become quite ubiquitous in the marketplace and attracted considerable interest amongst researchers, little research has investigated its effects on the brand equity of partners. The purpose of this paper is to demonstrate why and how brand alliance affects the brand equity of the partners in an alliance.

Design/methodology/approach

The hypotheses were tested by analysing the data of 260 participants in China, which were collected from an experiment.

Findings

This research draws five conclusions: the brand equity of a pre-alliance partner has a positive effect on brand alliance evaluation; product fit and brand fit amongst partners also have a positive effect on brand alliance evaluation; alliance brand evaluation has a positive impact on the brand equity of a post-alliance brand; the brand equity of a pre-alliance partner exerts a positive effect on the brand equity of a post-alliance partner; and the spillover effect of brand alliance for a weak brand is stronger than that of a strong brand in an asymmetrical brand alliance.

Originality/value

This research introduces brand equity into the field of brand alliance. From the perspective of consumer perception, the authors measure brand equity and provide insights for a company to effectively enhance brand equity through brand alliance. The authors explore ways to increase the brand equity of partners through brand alliance. Additionally, the authors discuss the spillover effects of the brand equity of partners in symmetric and asymmetric brand alliances.
Global human resources: a key to mission accomplishment
Authors: Wan Hooi Lai
Published: November 2018

Purpose

The purpose of this paper is to explore the factors needed for the development of global human resources for leadership assignments in foreign subsidiaries. The paper aims to find an answer to enhance expatriate mission accomplishment rate at subsidiaries abroad.

Design/methodology/approach

This study examines the development of global human resources. In-depth face-to-face interviews were employed to collect data from eight senior HR managers in three financial institutions in Taiwan, while data from 28 expatriates in the overseas subsidiaries were obtained from asynchronous e-mail interviews. Conventional content analysis was used to code categories directly from the data.

Findings

The results of the study revealed that organizational policies do not focus on developing global human resources. To portray a global image, the focus is on staffing overseas subsidiaries with foreigners and Taiwanese that can speak English. Development to prepare staff for expatriation is limited to pre-departure training that focused mainly on language and cultural awareness training. However, organizational support during expatriation and repatriation is important. Expatriates view security briefing crucial and familiarization visit helps them to decide whether or not to accept expatriation. Organizational policies favor those that were not expatriated in terms of career progression deter managers from accepting international assignments.

Originality/value

It highlights some best practices in developing global human resources taking into consideration the herd mentality and social perspective. Social support, social learning and social capital are instrumental in developing global human resources as these hasten cultural adjustment.
Exploring the connection between socially responsible HRM and citizenship behavior of employees in Indian context
Authors: Gahlawat Neha , Kundu Subhash C.
Published: November 2018

Purpose

The purpose of this paper is to establish the effectiveness of socially responsible HRM (SRHRM) on organizational citizenship behavior (OCB) while examining the mediating role of work motivation and job satisfaction.

Design/methodology/approach

Primary data based on 565 respondents belonging to various organizations operating in India were collected and analyzed. Statistical tools like confirmatory factor analysis and bootstrap procedure were used to determine the hypothesized relationships between SRHRM and employee attitudes and behavior.

Findings

Drawing upon social identity perspective, the results have revealed that the employees’ perceptions of SRHRM including legal compliance HRM, employee-oriented HRM, general corporate social responsibility (CSR) facilitation HRM and general CSR conduct are related to higher engagement in extra-role behavior among employees in Indian context. The findings further reveal that this SRHRM–OCB relationship is serially mediated by work motivation and job satisfaction.

Practical implications

The study gives strong indications that managers at both global and local level need to pay high attention to the designing and implementation of the CSR-focused HRM systems in their organizations, as these do not only lead to positive organizational image but also generate positive employee outcomes.

Originality/value

By establishing a multi-step partial mediation model, this study brings new insights in the underlying mechanism existing in the SRHRM–OCB relationship.
An explorative study of trends, distribution and pattern of bilateral cross-border joint ventures (CBJVs)
Authors: Dhir Sanjay , Mital Amita
Published: November 2018

Purpose

This paper aims to explore the trends, distribution and pattern of Indian bilateral cross-border joint venture (CBJV) activity with advanced developed nations (G7 nations) which include the USA, the UK, Japan, France, Germany, Italy and Canada over the 2001-2010 period.

Design/methodology/approach

Longitudinal data on the population of 201 CBJVs are analyzed using Securities Data Company (SDC) platinum database. Chi-square test of independence is conducted on the parameters for CBJVs collected over a span of 10 years to test interrelations between them.

Findings

The results of explorative trend analysis and test of interdependence are significantly different from developed countries in terms of interrelation between parent’s nationality, industry classification, broad purpose, period of formation and the equity owned.

Research/limitations implications

Future work may explore the strategic motivation of both developed and developing nation firms, given the dynamics of CBJVs explored in this paper. The study could also be extended to other developed and developing nation firms CBJVs with Indian firms.

Practical implications

This study provides a broad-based objective exploratory study of trends and distribution of CBJVs from the standpoint of the developing nations. This helps managers to identify the dynamic industries of CBJVs in India as far as G7 nations are concerned.

Social implications

The possibility of asymmetric motives of partners in CBJV could not be negated. The role of Indian policymakers also becomes much larger to regulate the monopolistic and anti-competitive practices.

Originality/value

The longitudinal study serves to present first of its kind systematic analysis of detailed activity of Indian firms in bilateral CBJV formation.
Modelling repurchase intention among smartphones users in Nigeria
Authors: Adekunle Simon Ayo , Ejechi Jones O.
Published: November 2018

Purpose

This study aims to model repurchase intention among smartphones users by using structural equation modelling. The model was used to determine the impact of service quality measured by convenience, functionality and perceived usefulness on users’ satisfaction and repurchase intention. The study also examined the mediating role of users’ satisfaction on repurchase intention.

Design/methodology/approach

A survey research design was adopted to gather data used for this study through questionnaire administration. In total, 500 copies of the questionnaire were administered to smartphones users in Nigeria, and 486 copies of the questionnaire were found usable for data analyses. The data obtained were analysed using different statistical tools such as mean, standard deviation, correlation, confirmatory factor analysis and structural equation modelling through the use of Analysis of Moment Structures software.

Findings

The study revealed that users’ satisfaction is significantly influenced by convenience, functionality and perceived usefulness. Similarly, repurchase intention is significantly impacted by perceived usefulness. The results further showed that there is a positive and statistically significant relationship between users’ satisfaction and repurchase intention. However, convenience and functionality were found to have positive but statistically insignificant relationship with repurchase intention.

Originality/value

This study contributes to the emerging discourse on the perception of smartphone users with respect to convenience, functionality, perceived usefulness, satisfaction and repurchase intention in the Nigerian context. It presents a latest attempt and useful insights on the service quality–users’ satisfaction–repurchase intention nexus among smartphone users in Nigeria.
Leadership of change in South Africa public sector turnarounds
Authors: Kumalo Mampe , Scheepers Caren Brenda
Published: November 2018

Purpose

Organisational decline has far-reaching, negative emotional and financial consequences for staff and customers, generating academic and practitioner interest in turnaround change processes. Despite numerous studies to identify the stages during turnarounds, the findings have been inconclusive. The purpose of this paper is to address the gap by defining these stages, or episodes. The characteristics of leaders affect the outcome of organisational change towards turnarounds. This paper focusses, therefore, on the leadership requirements during specific episodes, from the initial crisis to the full recovery phases.

Design/methodology/approach

A total of 11 semi-structured interviews were conducted with executives from the public sector in South Africa who went through or were going through turnaround change processes and 3 with experts consulting to these organisations.

Findings

Contrary to current literature in organisational change, this study found that, in these turnaround situations, leadership in the form of either an individual CEO or director general was preferable to shared leadership or leadership distributed throughout the organisation. This study found four critical episodes that occurred during all the public service turnarounds explored, and established that key leadership requirements differ across these episodes. The study shows how these requirements relate to the current literature on transactional, transformational and authentic leadership.

Practical implications

The findings on the leadership requirements ultimately inform the selection and development of leaders tasked with high-risk turnaround change processes.

Originality/value

Four episodes with corresponding leadership requirements were established in the particular context of public sector turnaround change processes.
Shift work – change from semi-continuous to continuous system
Authors: Silva Isabel Soares , Bastos Renata
Published: November 2018

Purpose

The purpose of this paper is to understand workers’ resistance toward change from a semi-continuous (SCW) to a continuous shift work system (CW), especially focusing the perspective of change and its impact on workers’ personal lives.

Design/methodology/approach

A case study was conducted at a Portuguese steel plant. A questionnaire was administered to 98 shift workers of the two systems, three focus groups (FG) each with ten CW workers, and three interviews with their managers.

Findings

The results of the FG and the interviews indicate the loss of days off during weekends as the main drawback of this change, leading to work schedule dissatisfaction. The consequences of the change focused on social and family life. For the CW workers, the conciliation between working hours and life outside the company were the only predictors of satisfaction with work schedule.

Research limitations/implications

The cross-sectional design is one of the main limitations, as well the use of only one organization in the study suggests future replication. Organizations need to consider the aspects of family and social life in the management of working hours.

Originality/value

Globally, this case study highlights the importance of family and social aspects in the adjustment process to working hours, especially when these involve performing work on the weekends, such as shift work.
A job resources-based intervention to boost work engagement and team innovativeness during organizational restructuring
Authors: Seppälä Piia , Hakanen Jari J. , Tolvanen Asko , Demerouti Evangelia
Published: November 2018

Purpose

The purpose of this paper is to investigate the effectiveness of a job resources-based intervention aimed at proactively increasing work engagement and team innovativeness during organizational restructuring using a person-centered approach.

Design/methodology/approach

The intervention was conducted in two organizations: two departments served as participants (n=82) and two as controls (n=52). The aim was to first identify sub-groups of employees with different developmental patterns of work engagement, and then to determine whether these sub-groups benefited differently from the intervention with respect to team innovativeness and work engagement.

Findings

Latent profile analysis identified three different patterns of work engagement among the participants: high and stable (n=64), moderate and decreasing (n=13), and low and decreasing (n=5). The χ²-test yielded no significant difference between participants and controls (n=52) with respect to team innovativeness over time. However, t-tests showed that team innovativeness increased in the high work engagement class and somewhat decreased in the moderate and low work engagement classes.

Practical implications

During organizational changes, those initially work-engaged seem to be able to proactively build their team innovativeness via a job resources-based intervention and remain engaged; whereas those initially not work-engaged may not, and their work engagement may even decrease.

Originality/value

This study reveals that an initial level of work engagement is a prerequisite why some employees profit more from a job resources-based intervention than others and provides tailored knowledge on the effectiveness of the intervention.
The relation between social isolation and increasing suicide rates in the elderly
Authors: Heuser Christoph , Howe Jürgen
Published: November 2018

Purpose

Suicidal attempts and thoughts are particularly relevant to the health of the elderly and can impact not only the individual, but family, friends and spouses as well. This topic is important for the gerontological research community, particularly as it relates to social isolation and the feeling of loneliness, common in this population group. The purpose of this paper is to investigate new knowledge about the relationship between an increased risk of suicide in the elderly and social isolation or loneliness.

Design/methodology/approach

An extensive search was conducted to find relevant studies to answer the research question. Database research was done in PubMed and PsycINFO for relevant studies within the last 10 years. The title and abstract of relevant articles were screened before the full-text was acquired.

Findings

In PubMed 163 studies were identified, and in PsycINFO 66 studies were identified. After a thorough screening, nine studies were found to be appropriate for this study.

Originality/value

It is not clear which risk factor leads to an increase in suicidal thoughts and attempts, however most studies contemplated loneliness and isolation as a covariant. A causal link between the concepts is not simple. Nevertheless, loneliness and isolation seem to be relevant factors for suicidal ideations.
Relationship between corporate social responsibility and tax avoidance: international evidence
Authors: Zeng Tao
Published: November 2018

Purpose

This paper aims to examine the relationship between corporate social responsibility (CSR) and tax avoidance as well as how CSR and country-level governance interplay in affecting tax avoidance in an international setting.

Design/methodology/approach

This paper is an empirical work using listed companies from 35 countries and relying on several proxies for corporate tax avoidance activities including the difference between the statutory tax rate and the annual effective tax rate, the book-tax difference and the residual book-tax difference.

Findings

This study finds strong evidence that CSR is positively related to tax avoidance. It also finds that in countries with weak country-level governance, firms with higher CSR scores engage in less tax avoidance, implying that CSR and country-level governance are substitutes.

Originality/value

This paper is the first study that examines the relationship between CSR and tax avoidance in an international setting with different legal and institutional environment.
Promoting positive communication environments: a service evaluation
Authors: Patel Kunden , Roche Laura , Coward Nicola , Meek Jacqueline , Harding Celia
Published: November 2018

Purpose

The purpose of this paper is to present an evaluation of a programme of training and support provided to staff, which aimed to encourage supported communication environments for people with learning disabilities.

Design/methodology/approach

Training, monitoring and support for communication, specifically augmentative and alternative communication (AAC) strategies, was provided by speech and language therapy staff to two residential services over 46 weeks. Staff and service user communications were observed pre- and post-intervention.

Findings

In one provision there was an increase in service user initiations and the use of some AAC strategies by support staff. In the other provision there was no change in service user initiations and a decrease in the range of AAC strategies used. It appears that some forms for AAC remain challenging for staff to implement.

Originality/value

This evaluation explores ways of using specialist support services to improve communication environments for people with learning difficulties. Possible reasons for differences in the outcome of the intervention are discussed. Future research into the types of communication interactions experienced by people with learning disabilities across the range of communication styles may be useful so that support staff can be better helped to provide sustained and enriched communication environments.
School absences and exclusions experienced by children with learning disabilities and autistic children in 2016/17 in England
Authors: Hatton Chris
Published: November 2018

Purpose

The purpose of this paper is to examine data on absences and exclusions from school amongst children with learning disabilities and autistic children in England in 2016/2017.

Design/methodology/approach

Data were drawn from Department for Education statistics for the school year 2016/2017 on school absences (authorised and unauthorised) and school exclusions (fixed-period and permanent) for children in the primary special educational needs categories of moderate learning difficulty (MLD), severe learning difficulty (SLD), profound and multiple learning difficulty (PMLD) and autistic spectrum disorder (ASD).

Findings

Authorised school absence rates were higher for all groups of children investigated compared to children without special educational needs, primarily due to illnesses and health-related appointments. Rates of unauthorised school absences were low. Rates of fixed-period and permanent school exclusions were higher for children with MLD and ASD compared to children without SEN, and lower for children with SLD and PMLD. Reasons given for exclusions were similar across children (persistent disruptive behaviour, physical assault against a pupil, verbal abuse against an adult), although physical assault against an adult was also commonly mentioned for children with SLD, PMLD or ASD.

Social implications

Reducing school absences for children with learning disabilities and autistic children will involve co-ordination of health and social care support arrangements to ensure they are convenient and efficient for children and families. In terms of exclusions, schools need to consider the extent to which they are making reasonable adjustments for children with learning disabilities and autistic children.

Originality/value

This paper presents in one place statistics concerning school absences and school exclusions for children with learning disabilities and autistic children in England.
Neuropsychological changes in patients with substance use disorder after completion of a one month intensive outpatient treatment program
Authors: McKowen James W. , Isenberg Benjamin M. , Carrellas Nicholas W. , Zulauf Courtney A. , Ward Nalan E. , Fried Ronna S. , Wilens Timothy E.
Published: November 2018

Background and Objectives

Data suggest individuals with substance use disorders (SUD) exhibit high rates of executive functioning (EF) impairment, and that EF level can predict treatment retention. The primary aim of the present study was to investigate if patients who completed a 1 month intensive outpatient program (IOP) for SUD demonstrated recovered EF.

Methods

Baseline and follow‐up neurocognitive functioning was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the self‐reported Behavior Rating Inventory of Executive Functioning (BRIEF‐A) questionnaire.

Results

The final sample included 15 patients who completed the one month IOP and for whom data were available (53% male, aged 36 years ± 13.4). Despite exhibiting general improvements in EF and significant improvements in organization, subjects continued to manifest significant executive dysfunction as evaluated by self‐report and computerized assessment.

Conclusions and Scientific Significance

Patients with SUD often manifest high levels of executive dysfunction upon entry into SUD treatment that, while improving minimally, appears to persist despite intensive outpatient treatment at 1 month. These persistent EF deficits may affect patient engagement and participation in treatment, thus necessitating SUD programs to assess and accommodate EF issues throughout treatment. (Am J Addict 2018;XX:1–7)
A Portfolio Optimization Approach with a Large Number of Assets: Applications to the US and Korean Stock Markets
Authors: Lee Miyoung , Kim Jihun , Oh Sekyung
Published: November 2018

We propose a new approach for determining optimal portfolio weights in a mean‐variance framework in cases when there are more assets than observations. We empirically show that our approach attains a higher out‐of‐sample Sharpe ratio, M2 measure, and CEQ return than other methods. Our approach is also free from problems related to the estimation of the covariance matrix because it does not need and solves the so‐called “corner‐solution problem” of the Markowitz model by minimizing the 2‐norm of the portfolio weight vector.
The analgesic effects of intrathecal morphine in comparison with ultrasound‐guided transversus abdominis plane block after caesarean section: a randomised controlled trial at a Ugandan regional referral hospital
Authors: Kwikiriza A. , Kiwanuka J. K. , Firth P. G. , Hoeft M. A. , Modest V. E. , Ttendo S. S.
Published: November 2018

Both transversus abdominis plane block and intrathecal morphine may produce prolonged postoperative analgesia, but the respective clinical outcomes of these anaesthetic techniques in resource‐limited settings are not well described. We randomly assigned patients undergoing caesarean section to receive a hyperbaric bupivacaine (10 mg) spinal anaesthetic followed by an ultrasound‐guided transversus abdominis plane block, or a hyperbaric bupivacaine (10 mg) spinal anaesthetic with 100 mcg intrathecal morphine, followed by a postoperative sham block. Supplemental postoperative analgesia included self‐administered oral diclofenac 50 mg and paracetamol 1 g every 8 h. Numerical pain rating scores, the need for rescue medication, side‐effects and patient satisfaction were recorded at 8, 16 and 24 h. We enrolled a total of 130 patients, with 65 women in each group. The mean numerical rating score for intrathecal morphine vs. transversus abdominis plane blocks at 8 h were: at rest, 2.5 vs. 3.1 (p = 0.04); with coughing, 4.3 vs. 4.8 (p = 0.07); and with movement, 3.6 vs. 4.2 (p = 0.06). At 16 h, respective scores were: 2.9 vs. 3.1 (p = 0.40) at rest; 4.0 vs. 4.3 (p = 0.19) with coughing; and 4.8 vs. 5.0 (p = 0.33) with movement. At 24 h, the respective scores were: 2.9 vs. 2.3 (p = 0.01); 4.6 vs. 4.2 (p = 0.04) with coughing; and 3.9 vs. 3.4 (p = 0.02) with movement. The need for rescue medication and the incidence of pruritis, sedation and nausea and vomiting were similar in both groups. Patient satisfaction with pain control was similar in both groups, with the majority of patients reporting satisfaction as good or excellent. Intrathecal morphine and transversus abdominis plane block provided clinically similar outcomes for pain relief after caesarean section.
Design, synthesis, and biological evaluation of thieno[3,2‐d]pyrimidine derivatives as potential simplified phosphatidylinositol 3‐kinase alpha inhibitors
Authors: Yang Xiuyan , Deng Meng , Zhang Xi , Wang Yi , Song Kun , Cong Ruan , Meng Linghua , Zhang Jian
Published: November 2018

A series of thieno[3,2‐d]pyrimidine derivatives as phosphatidylinositol 3‐kinase (PI3K) inhibitors was designed using the combination strategy. The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3K, culminating in the discovery of 7 and 21. Determination of a co‐crystal structure of 7 complexed with PI3Kα provided the structural basis for the high enzymatic activity. Furthermore, cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mammalian target of rapamycin pathway. The results provided potent simplified inhibitors of PI3K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.
Discovery of potent HIV‐1 non‐nucleoside reverse transcriptase inhibitors by exploring the structure–activity relationship of solvent‐exposed regions I
Authors: Kang Dongwei , Wang Zhao , Chen Meng , Feng Da , Wu Gaochan , Zhou Zhongxia , Jing Lanlan , Zuo Xiaofang , Jiang Xiangyi , Daelemans Dirk , De Clercq Erik , Pannecouque Christophe , Zhan Peng , Liu Xinyong
Published: November 2018

Two novel series of human immunodeficiency virus‐1 (HIV‐1) non‐nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2‐d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild‐type (WT) HIV‐1 strain in MT‐4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV‐1. Compound 7 (EC50 = 0.014, 0.031 μM) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50 = 7.572, 0.190 μM) and comparable to that of etravirine (ETV, EC50 = 0.004, 0.014 μM). Molecular docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.
MedPServer: A database for identification of therapeutic targets and novel leads pertaining to natural products
Authors: Potshangbam Angamba Meetei , Polavarapu Raja , Rathore Ravindranath Singh , Naresh Damuka , Prabhu Nagu Prakash , Potshangbam Nongdam , Kumar Pravind , Vindal Vaibhav
Published: November 2018

Natural products have been the source of treatment for various human diseases from time immemorial. Interests in natural product‐based scaffolds for the discovery of modern drugs have grown in recent years. However, research on exploring the traditional medicinal systems for modern therapeutics is severely limited due to our incomplete understanding of the therapeutic mechanism of action. One possible solution is to develop computational approaches, based on ligand‐ and structure‐based screening tools, for fast and plausible target identification, leading to elucidation of the therapeutic mechanism. In the present work, we present two methods based on shape‐based and pharmacophore search to predict targets of natural products and elucidate their mechanism, and to identify natural product‐based leads. These methods were tested on an in‐house developed database of medicinal plants that include information from a largely unexplored North‐East region of India, known as one of the twelve mega biodiversity regions. However, depending on the choice of the lead molecules, any existing databases can be used for screening. MedPServer is an open access resource available at http://bif.uohyd.ac.in/medserver/.
Preliminary application of micro‐SPECT/CT imaging by 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met for non‐small‐cell lung cancer
Authors: Zhang Yiqiu , Meng Lanfang , Li Beilei , Tan Hui , Lin Qing‐Yu , Cheng Dengfeng , Shi Hongcheng
Published: November 2018

Objective

A novel 99mTc‐tricine‐EDDA‐Hynic‐c‐Met molecular probe was synthetized, and nude mice models of human non‐small‐cell lung cancer (NSCLC) were established in order to preliminarily investigate that whether the molecular probe can be used to screen c‐Met inhibitor for targeted drug therapy in NSCLC.

Methods

With Hynic as the chelating agent, 99mTcO4‐labeled c‐Met receptor was used to synthetize 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met. Two nude mice successfully transplanted with H1993 tumor and two nude mice transplanted with H292 tumor were injected with 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met through the tail vein. After 2 and 4 hr, micro‐SPECT/CT imaging was performed.

Results

micro‐SPECT/CT imaging of nude mice transplanted with H1993 and H292 tumors using 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met showed that uptake of 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met was high in H1993 tumor, while it was mild in H292 tumor both at 2 and 4 hr postinjection. Semiquantitative analysis of the ratio of radioactivity intensity at tumor site to radioactivity intensity of adjacent muscles (T/N value) showed that the average T/N value of H1993 and H292 tumors at 2 hr was 3.90 and 2.85, while it was 4.88 and 2.36 at 4 hr.

Conclusion

micro‐SPECT/CT imaging through 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met can be used to screen c‐Met indicators of NSCLC in H1993 nude mice models for targeted drug therapy.
The peripheral immune response after stroke—A double edge sword for blood‐brain barrier integrity
Authors: Li Yan , Zhu Zi‐Yu , Huang Ting‐Ting , Zhou Yu‐Xi , Wang Xin , Yang Li‐Qun , Chen Zeng‐Ai , Yu Wei‐Feng , Li Pei‐Ying
Published: November 2018

The blood‐brain barrier (BBB) is a highly regulated interface that separates the peripheral circulation and the brain. It plays a vital role in regulating the trafficking of solutes, fluid, and cells at the blood‐brain interface and maintaining the homeostasis of brain microenvironment for normal neuronal activity. Growing evidence has led to the realization that ischemic stroke elicits profound immune responses in the circulation and the activation of multiple subsets of immune cells, which in turn affect both the early disruption and the later repair of the BBB after stroke. Distinct phenotypes or subsets of peripheral immune cells along with diverse intracellular mechanisms contribute to the dynamic changes of BBB integrity after stroke. This review focuses on the interaction between the peripheral immune cells and the BBB after ischemic stroke. Understanding their reciprocal interaction may generate new directions for stroke research and may also drive the innovation of easy accessible immune modulatory treatment strategies targeting BBB in the pursuit of better stroke recovery.
Effects of Common CYP1A2 Genotypes and Other Key Factors on Intraindividual Variation in the Caffeine Metabolic Ratio: An Exploratory Analysis
Authors: Tian Dan‐Dan , Natesan Senthil , White John R. , Paine Mary F.
Published: November 2018

The caffeine metabolic ratio is an established marker for cytochrome P450 (CYP) 1A2 activity. Optimal sample size calculation for clinical pharmacokinetic xenobiotic–caffeine interaction studies requires robust estimates of interindividual and intraindividual variation in this ratio. Compared with interindividual variation, factors contributing to intraindividual variation are less defined. An exploratory analysis involving healthy nonsmoking non‐naïve caffeine drinkers (1–3 cups/day; 12 men, 12 women) administered caffeine (160 mg) on five occasions evaluated the effects of CYP1A2 induction status (based on genotype) and other factors on intraindividual variation in CYP1A2 activity. Results were compared with those from previous studies. Regardless of whether a hyperinducer (CYP1A2*1A/*1F or CYP1A2*1F/*1F) or normal metabolizer (CYP1A2*1A/*1A, CYP1A2*1C/*1F, or CYP1A2*1C*1F/*1C*1F), sex, age, oral contraceptive use by women, and smoking status, intraindividual variation was ≤30%. A value of 30% is proposed for optimal design of pharmacokinetic xenobiotic–caffeine interaction studies. Prospective studies are needed for confirmation.
Efficiency under Uncertainty and Non‐convexity: Evaluating the Role of Probabilities
Authors: Chavas Jean‐Paul , Briec Walter
Published: November 2018

This paper investigates the economics of uncertainty using a state‐contingent approach with a focus on the role of non‐convexity. Under efficiency, the slopes of a separating hypersurface measures state‐contingent prices. As argued by Yaari, normalized state‐contingent prices provide a measure of subjective probabilities. But efficiency under non‐convexity can require non‐linear pricing. The analysis identifies non‐convexity conditions under which probability assessments are not appropriate. Implications for economic and welfare analysis under uncertainty are discussed.
Letter to the Editor: Evidence‐based farriery – does it exist?
Authors: Coughlan N. E. , Cuthbert C. , O′Sullivan C. , McSweeney D.
Published: November 2018

See Editorial by Weller et al
Long‐term regular dental attendance and tooth retention among British adults: A cross‐sectional analysis of national survey data
Authors: Talakey Arwa Ameen , Bernabé Eduardo
Published: November 2018

Objective

To explore the association between long‐term pattern of dental attendance and tooth retention among British adults.

Methods

This study analysed data from 2970 dentate adults who participated in the Adult Dental Health Survey. Data were collected through home interviews and clinical examinations. Individuals were categorized into four trajectories according to their responses to three questions on dental attendance over their life span. The four trajectories were always, current, former and never regular attenders. Tooth retention was measured as the number of natural teeth retained and having a functional dentition (20 or more teeth). Associations were examined in regression models adjusted for demographic (sex, age and country of residence), socioeconomic (education, equivalized household income and social class) and clinical factors (untreated caries and periodontal disease).

Results

Never and former regular attenders had fewer teeth retained (rate ratios with 95% confidence interval: 0.93 [0.89‐0.97] and 0.97 [0.96‐0.99], respectively) and lower odds of having functional dentition (odds ratios with 95% CI: 0.36 [0.22‐0.60] and 0.53 [0.34‐0.83], respectively) than always regular attenders after adjusting for demographic, socioeconomic and clinical characteristics. However, no differences in number of teeth retained or having a functional dentition were found between always and current regular attenders.

Conclusion

Long‐term regular dental attendance was associated with greater tooth retention. Never and former regular attenders had fewer teeth retained than always regular attenders. No difference in tooth retention was found between always and current regular attenders.
Thermal and crystallization behavior of SiO2‐PbF2 glass system in the presence of ErF3 and Al2O3
Authors: Torab Ahmadi Pooya , Eftekhari Yekta Bijan , Mohammadi Hesameddin , Golestani‐Fard Farhad
Published: November 2018

Oxyfluoride glass‐ceramics have been introduced as one of the best bulk hosts for upconversion process of rare‐earth ions. However, less attention to the technological topics in the process of glass crystallization has hindered the development of them in industrial scale applications. In this research, SiO2–PbF2 glasses were investigated to clarify the ambiguous role of rare‐earth ions and alumina content in the microstructure and crystallization behavior. Results indicated that Er3+ addition caused a liquid‐liquid phase separation via nucleation and growth mechanism, which led to single phase crystallization of β‐PbF2:Er3+ solid solution. Moreover, Er3+ had a significant effect on the crystallite size, size distribution, and PbF2 crystallization temperature. On the other hand, increasing Al2O3 content enhanced the transparency and thermal stability of glass samples, whereas it reduced the amount of fluorine loss and increased the dissolution of Er3+ in fluoride crystalline structure. These results address some of the most controversial issues about crystallization behavior of rare‐earth‐doped oxyfluoride glasses.
Dynein axonemal intermediate chain 2 plays a role in gametogenesis by activation of Stat3
Authors: Yang Zhaojuan , Xu Bo , Hu Xiaopeng , Yao Xiaoying , Tang Yunhui , Qian Cuifeng , Wang Shuzeng , Chen Haifeng , Bai Xiaohui , Wu Ji
Published: November 2018

We previously identified the mouse dynein axonemal intermediate chain 2 (Dnaic2) gene. This gene expresses a component of the axonemal dynein complex that functions in cilia or flagella. We found that overexpression of Dnaic2 results in female subfertility and male infertility. In this study, we generated Dnaic2 knockdown (KD) mice and identified the potential regulatory mechanisms involved in Dnaic2 function. For phenotype analysis, we found that body weight was lighter and size was smaller in Dnaic2 KD mice than in wild‐type mice. A total of 45% of these Dnaic2 KD mice were infertile due to sperm abnormalities in males, or had oocyte abnormalities and pathological changes in the tunica mucosa in the oviduct of females. Moreover, Dnaic2 overexpression enhanced the expression of proliferating cell nuclear antigen (PCNA) in the ovaries, which suggested that Dnaic2 stimulated proliferation of cells in the ovaries. However, PCNA expression in the testis of Dnaic2‐overexpressed mice was lower than that in controls. Additionally, the ratio of Bax/B‐cell lymphoma‐2(Bcl‐2) in the testis of Dnaic2‐overexpressed mice was higher than that in controls, which suggested that Dnaic2 inhibited cellular proliferation in the testis. To examine the molecular action of Dnaic2, immunoprecipitation analysis was used and showed that Dnaic2 protein interacted with signal transducer and activator of transcription 3 (Stat3). Molecular modelling analysis showed that Dnaic2 bound with the linker and SH2 domains of Stat3. Furthermore, overexpression of Dnaic2 promoted phosphorylation of Stat3. In conclusion, our study suggests that Dnaic2 plays a role in oogenesis and spermatogenesis by activation of Stat3.
High health care costs among adults with intellectual and developmental disabilities: a population‐based study
Authors: Lunsky Y. , De Oliveira C. , Wilton A. , Wodchis W.
Published: November 2018

Objective

While it is generally accepted that adults with intellectual and developmental disabilities (IDDs) use health services to a greater extent than the general population, there is remarkably little research that focuses on the costs associated with their health care. Using population‐based data from adults with IDD in Ontario, this study aimed to estimate overall health care costs, classify individuals into high and non‐high cost categories and describe differences in the demographics, clinical profiles and health care use patterns between these groups.

Design

A retrospective cohort study based in Ontario, Canada, was conducted with the use of linked administrative health data.

Methods

A costing algorithm developed for the general population in Ontario was applied to estimate health care costs of adults with IDD under age 65 for 2009 and 2010. Individuals were categorised into two groups according to whether their total annual health care costs were among the highest decile in the general population. These groups were compared on demographic and clinical variables, and relative mean costs for six types of health care services in the two groups were computed. In addition, we computed the proportion of individuals who remained in the high cost group over 2 years.

Results

Among adults with IDD, 36% had annual health care expenditures greater than $2610 CAD (top decile of all Ontario adults under 65). These individuals were more likely to be female, to be in the oldest age groups, to live in group homes and to be receiving disability income support than individuals whose expenditures were below the high cost threshold. In addition, they had higher rates of all the physical and mental health conditions studied. Greatest health care expenses were due to hospitalisations, especially psychiatric hospitalisations, continuing care/rehabilitation costs and medication costs. The majority of individuals whose health care costs placed them in the high cost category in 2009 remained in that category a year later.

Discussion

Adults with IDD are nearly 4 times as likely to incur high annual health care costs than those without IDD. Individuals with IDD and high health care costs have unique health and demographic profiles compared with adults with IDD whose annual health care costs are below the high cost threshold. Attending to their health care needs earlier in their health care trajectory may be an opportunity to improve health and reduce overall health care costs. It is important that we explore how to best meet their needs. Models proposed to meet the needs of adults with high health care costs in the general population may not apply to this unique group.