bluuebunny/crossref_metadata_2025 huggingface dataset:
Is pharmacist pre-registration training equitable and robust?
Authors: Jee Samuel David , Schafheutle Ellen Ingrid , Noyce Peter Raymond
Published: January 2019

Purpose

Against a backdrop of concerns regarding the quality and equity of the final practice-based pre-registration training year, the purpose of this paper is to examine how robust and equitable current education and training arrangements in Great Britain are in preparing newly qualified pharmacists (NQPs) for practice.

Design/methodology/approach

In addition to considering relevant regulator, policy and research literature, this paper presents findings from a longitudinal qualitative study that tracked 20 pharmacy trainees and their tutors during pre-registration training and early registered practice. Trainees were interviewed four times over a 12-month period; tutors were interviewed twice. Semi-structured interviews explored learning and development, work environment and support received. Interview transcripts were analysed thematically using template analysis.

Findings

Currently, there are no requirements tor training pre-registration tutors, or for accreditation or quality assurance of training sites. Longitudinal interview findings showed that community trainees developed knowledge of over-the-counter and less complex, medicines whereas hospital trainees learnt about specialist medicines on ward rotations. Hospital trainees received support from a range of pharmacists, overseen by their tutor and other healthcare professionals. Community trainees generally worked within a small pharmacy team, closely supervised by their tutor, who was usually the sole pharmacist. NQPs were challenged by having full responsibility and accountability as independent practitioners, without formal support mechanisms.

Originality/value

The variability in trainee experience and exposure across settings raises concerns over the robustness and equity of pre-registration training. The lack of formal support mechanisms post-registration may pose risks to patient safety and pharmacists’ well-being.
Practice-based learning in the Tequila industry: the business school goes out of the classroom
Authors: Toledano-O’Farrill Ruben
Published: January 2019

Purpose

The purpose of this paper is to present the methodology and results of practice-based learning in the Business School of a higher education institution (HEI) in Mexico, with a focus on students’ participation and learning experience.

Design/methodology/approach

This research is a descriptive and qualitative analysis of six team experiences within a larger project developed through university–business partnership with the aim of helping develop organizational capabilities of small and medium enterprises within the Tequila industry in Mexico.

Findings

Participation of students in project-based learning, in genuine scenarios alongside professional consultants, is an effective way to develop learning and to apply prior knowledge. Learning occurs at several levels, including developing professional knowledge, teamwork, leadership and communication skills, and to some extent consulting skills. Client organizations also develop learning in work-based learning (WBL) projects.

Research limitations/implications

The research methodology does not allow for generalization of the results on a large scale.

Practical implications

This research shows a successful instance of project- and practice-based learning that may be helpful for HEIs seeking to implement this learning methodology.

Social implications

There is research evidence that more students are expecting to get practice-based skills as part of their higher education training. This paper supports the argument that HEIs can develop wide scale WBL programs that have impact on students’ learning and skills development as well as on the development of host organizations.

Originality/value

The instance of WBL described in this research paper is unique within HEIs in Mexico.
Choke flutter instability sources tracking with linearized calculations
Authors: Duquesne Pierre , Rendu Quentin , Aubert Stephane , Ferrand Pascal
Published: January 2019

Purpose

The choke flutter is a fluid-structure interaction that can lead to the failure of fan or compressor blade in turbojet engines. In ultra high bypass ratio (UHBR) fans, the choke flutter appears at part-speed regimes and at low or negative incidence when a strong shock-wave chokes the blade to blade channel. The purpose of this study is to locate the main excitation sources and improving the understanding of the different work exchange mechanisms. This work contributes to avoiding deficient and dangerous fan design.

Design/methodology/approach

In this paper, an UHBR fan is analyzed using a time-linearized Reynolds-averaged Navier–Stokes equation solver to investigate the choke flutter. The steady-state and the imposed vibration (inter blade phase angle, reduced frequency and mode shape) are selected to be in choke flutter situation. Superposition principle induced by the linearization allow to decompose the blade in numerous small subsections to track the contribution of each local vibration to the global damping. All simulations have been performed on a two-dimensional blade to blade extraction.

Findings

Result analysis points to a restricted number of excitation sources at the trailing edge which induce a large part of the work exchange in a limited region of the airfoil. Main phenomena suspected are the shock-wave motion and the shock-wave/boundary layer interaction.

Originality/value

An original excitation source tracking methodology allowed by the linearized calculation is addressed and applied to a UHBR fan test case.
An exploration into the problematic public policies and the leadership challenge for socio-economic transformation in South Africa
Authors: Ndalamba Ken Kalala
Published: January 2019

Purpose

This paper aims to explore the problematic of public policies and leadership challenges for socio-economic transformation in South Africa. The paper illustrates that policies and laws of socio-economic reform have been introduced in democratic South Africa. However, socio-economic transformation remains a challenge. Lack of trust in the leadership relationships amongst political and economic agents is pointed as a contributing factor. Hence, LE emerges as a leadership strategy to help mitigate the problem.

Design/methodology/approach

The paper starts by presenting the current economic situation of South Africa touching on some important economic indicators to illustrate the consequences of poor leadership in public policy implementation process. The paper then analyses the leadership challenges to drive socio-economic reforms that have been introduced in South Africa since the end of apartheid with focus on the current National Development Plan. Lack of trust in leadership is identified as a problematic factor and leadership ethos (LE) emerges as a leadership strategy to enable the building of trust in leadership for the purpose of a successful implementation of public policies.

Findings

Lack of trust in leadership is identified as a problematic factor contributing in the absence of cooperation and collaboration in the leadership relationship amongst public servants (from up to bottom) and citizens for the purpose of successful implementation of public policies. Hence, there is need for a new leadership paradigm that would enable the building of trust in these leadership relationships. LE emerges as such a leadership strategy.

Practical implications

The paper calls for an exploration into the understanding and practice of LE and its inherent critical success factors (CSFs) considered as a leadership strategy that can help drive particularly public policies implementation process. LE intends to promote moral leadership that helps public servants to build good character and thus the will to do the right thing, and mutually trusting relationship is a CSF of LE. Therefore LE enables build the much needed trust in leadership relationships for a successful organisational leadership and management.

Originality/value

This paper provides significant implications by identifying lack of trust as a problematic factor in the leadership relationships amongst political and economic agents in South Africa, contributing thus in the poor implementation of public policies. LE emerges as a leadership strategy that would help mitigate the problem by enabling the building, the maintenance and restoration of trust in organisational and or institutional management for a successful public policy implementation process.
“Happy-performing managers” thesis
Authors: Hosie Peter , Sharma Piyush , Kingshott Russel P.J.
Published: January 2019

Purpose

The purpose of this paper is to extend the “Happy-Performing Managers” thesis to show that managers’ job-related affective well-being and affective job satisfaction mediate the impact of their role stressors (ambiguity, conflict and overload) on their contextual job performance.

Design/methodology/approach

Results from an online survey of 305 managers from the private, public and third sectors in Western Australian support most of the hypotheses. The psychometric properties of all the scales were analysed using confirmatory factor analysis and the conceptual model was tested using structural equation modelling.

Findings

Role stressors have a direct negative effect on the managers’ affective well-being and affective job satisfaction, which, in turn, mediate the negative effects of the three role stressors on the managers’ contextual performance.

Research limitations/implications

Conceptual and managerial contributions along with methodological limitations and future research directions are discussed.

Originality/value

Contemporary managers face a wide range of intrinsic and extrinsic role and environmental stressors. This research suggests that organisations may need to redesign manager roles to reduce their role stressors (ambiguity, conflict and overload) in order to optimise their contextual performance.
The long-term effect of training and development investment on financial performance in Korean companies
Authors: Kwon Kibum
Published: January 2019

Purpose

The purpose of this paper is to examine the relationship between training and development investment and financial performance over time. Human capital literature suggests that training and development investment may not immediately affect financial performance but may instead create effects that are realized over time. However, most existing cross-sectional research explores the influence of training and development investment on performance while overlooking training and development investment’s long-term effects.

Design/methodology/approach

This study focuses on the recovery period following the Great Recession circa 2008 in the South Korean business context. Longitudinal data from 312 firms, including four distinct waves, were used. Latent growth modeling was used to help identify a pattern of reciprocal relationships between training and development investment and financial performance over time.

Findings

The results indicate that even though growth in training and development investment is stable over time, there are significant between-firm differences in training and development investment trajectories over time. Prior financial performance was shown to be positively related to higher levels of training and development investment, but it was not related to growth in training and development investment. The initial level of training and development investment did not predict subsequent profit, but growth in training and development investment was positively related to future financial performance.

Originality/value

This study suggests that as an organization’s training and development investment increases over time, a delayed effect on financial performance may emerge because of this accumulated investment. Ultimately, the results highlight the importance of having a stock of human capital, rather than concentrating upon momentary flows that yield immediate effects.
Determining the structure of pharmaceutical industry in Iran
Authors: Emamgholipour Sara , Agheli Lotfali
Published: January 2019

Purpose

As the pharmaceutical industry is one of the key sectors of the health-care system, the identification of its structure is of particular importance. This paper aims to determine the structure of the pharmaceutical industry in Iran to provide appropriate solutions for pricing and regulation by policymakers. Iran is a growing pharmaceutical market with over $4bn in sales, so the supply side needs to be examined to meet the domestic consumption.

Design/methodology/approach

This research is a descriptive and retrospective analytical study which examines the Iranian pharmaceutical industry through library studies and using pharmaceutical data of the country’s Food and Drug Administration during 1992-2016. Due to data availability in firm level, the concentration ratio of N leading firms and the Herfindahl–Hirschman index are used to measure the concentration of the pharmaceutical market in 2014 and 2016.

Findings

The results show that pharmaceutical manufacturing, importing companies and distributing companies play roles in monopolistic competition market, loose oligopoly market and oligopoly market, respectively. For all companies, the magnitudes of Herfindahl–Hirschman indices indicate non-competitive settings. As a result, these companies set their own prices, and market demand affects their sales. In addition, demand for medicines is shaped in the form of supply-induced demand.

Research limitations/implications

This research was accomplished with no computational limitation. However, it was confined to only one country, one industry and the mentioned period of study.

Practical implications

The pharmaceutical manufacturers have no influence on medicine prices, and government pricing regulations lessen the market power of such market agents. However, the easy entry to and exit from market stimulate producers to participate in manufacturing activities. The pharmaceutical importers may expand their imports in response to entry new actors; however, the new entrants weaken the coordination on pricing decisions.

Social implications

As pharmaceutical distributers act in an oligopoly market, they can collude, reduce competition and lower the welfare of pharmaceutical consumers. In such conditions, high investment requirements and economies of scale may discourage the entry of new firms.

Originality/value

Although there are various studies on market structure in non-pharmaceutical industries, this study is a new effort to measure concentration in the Iranian pharmaceutical market and to determine its structure.
Machine criticality assessment for productivity improvement
Authors: Gopalakrishnan Maheshwaran , Skoogh Anders , Salonen Antti , Asp Martin
Published: January 2019

Purpose

The purpose of this paper is to increase productivity through smart maintenance planning by including productivity as one of the objectives of the maintenance organization. Therefore, the goals of the paper are to investigate existing machine criticality assessment and identify components of the criticality assessment tool to increase productivity.

Design/methodology/approach

An embedded multiple case study research design was adopted in this paper. Six different cases were chosen from six different production sites operated by three multi-national manufacturing companies. Data collection was carried out in the form of interviews, focus groups and archival records. More than one source of data was collected in each of the cases. The cases included different production layouts such as machining, assembly and foundry, which ensured data variety.

Findings

The main finding of the paper is a deeper understanding of how manufacturing companies assess machine criticality and plan maintenance activities. The empirical findings showed that there is a lack of trust regarding existing criticality assessment tools. As a result, necessary changes within the maintenance organizations in order to increase productivity were identified. These are technological advancements, i.e. a dynamic and data-driven approach and organizational changes, i.e. approaching with a systems perspective when performing maintenance prioritization.

Originality/value

Machine criticality assessment studies are rare, especially empirical research. The originality of this paper lies in the empirical research conducted on smart maintenance planning for productivity improvement. In addition, identifying the components for machine criticality assessment is equally important for research and industries to efficient planning of maintenance activities.
Reconceptualizing value innovation for Industry 4.0 and the Industrial Internet of Things
Authors: Matthyssens Paul
Published: January 2019

Purpose

Starting from the foundations of value innovation, this paper aims to give an idea of the key drivers and barriers – internal and external to the company – and to provide insight into proven capabilities underscoring the ability to create a flow of new value initiatives. These thoughts are then confronted with the present challenges of Industry 4.0 and the Industrial Internet of Things (IIoT). The confrontation leads to the identification of five capabilities for future-proof value innovation.

Design/methodology/approach

Literature review based upon the work of the author with more than two decades of experience within value innovation research is included. The review is supplemented with recent literature and an overview of the challenges of Industry 4.0/IIoT, which leads into a confrontation of the present status of value innovation with future requirements.

Findings

Value innovation remains important specifically for established companies facing path-breaking digital disruption of their existing business models provoked by Industry 4.0 and IIoT. Five key capabilities are suggested to rejuvenate value innovation and prepare it for the Industry 4.0 challenge: capabilities for designing, adapting and marketing product service systems; capabilities for blending digital strategy and processes with value offerings; capabilities for designing and mobilizing ecosystems and integrating these into a value-based IIoT platform; capabilities for combining and integrating technological and value innovation approaches; and capabilities for linking value creation to value capturing.

Research limitations/implications

This paper is more of a “viewpoint” than an empirically based paper presenting new research findings. It is based on expert judgment and confrontation with extant literature. The outlook indicating five key capabilities needs further empirical corroboration.

Practical implications

The overview of barriers and the “toolkit” for value innovation (Figure 1) and the five capabilities for future value innovation are expected to be managerially relevant.

Originality/value

The paper highlights the concept of value innovation, as discussed over the past decades, and links it to recent challenges and opportunities imposed by Industry 4.0 and the IIoT. The concept of value or strategic innovation is still valid but needs a re-conceptualization in view of these developments. The paper provides five capabilities business marketers should develop to perform value innovation in an Industry 4.0 environment.
Parameterization of biodiversity–productivity relationship and its scale dependency using georeferenced tree‐level data
Authors: Luo Weixue , Liang Jingjing , Cazzolla Gatti Roberto , Zhao Xiuhai , Zhang Chunyu
Published: January 2019

The biodiversity–productivity relationship (BPR) constitutes one of the most fundamental yet challenging topics in ecology. Most described BPRs so far are based on relatively small grain sizes (typically smaller than 1ha), and understanding how the BPRs scale up from individual trees to communities of different sizes, a mission critical for biodiversity conservation and forest management, still remains elusive.

Based on a unique 54.12‐ha large‐scale forest observational site in Northeastern China, where we georeferenced and measured approx. 90,000 trees in two consecutive inventories, we studied BPRs across a cascade of spatial scales using geostatistical analysis and bootstrapping. To explore the underlying mechanisms of the scale dependency of BPR, we further investigated the scale gradient in biodiversity and productivity, respectively, and assessed neighbourhood influences on individual trees.

Across all the spatial scales, we found a consistent positive concave‐down effect of tree species richness on forest productivity. The elasticity of substitution (θ) represented the degree to which species can substitute for each other in contributing to forest productivity. At the community level, the curvature of BPRs in terms of the elasticity of substitution (θ) declined from around 0.50 and converged at around 0.15, as the grain size increased from 0.01 to 1.00 ha, all else being equal. Similarly, at the individual tree level, neighbourhood diversity coefficient, a linear proxy of θ, declined from around 0.08 and converged at around 0.03, as neighbourhood size increased from 0.01 to 1.00 ha, all else being equal.

Synthesis. Our study found a pronounced scale dependency of biodiversity–productivity relationship and quantified, for the first time, how biodiversity–productivity relationship scale up from 0.01 to 1.00 ha. Our findings suggest that biodiversity–ecosystem functioning relationship can be generally scale‐dependent and, hence, one must factor in this effect in biodiversity conservation and ecological restoration projects. Our findings also indicate that biodiversity–productivity relationship, predominantly determined by biological processes (i.e. complementarity and diminishing marginal productivity) at a small scale, can be increasingly influenced by statistical (i.e. spatial central limit theorem) and other (such as species–area relationship) processes as the scale increases.
Local and biogeographic determinants and stochasticity of tree population demography
Authors: Mori Akira S.
Published: January 2019

Demographic events such as the birth and death of organisms are ubiquitous in nature. Disentangling the processes that underlie the demographic dynamics of species is fundamental to understanding how biodiversity is organized and will be re‐organized at multiple scales.

To provide new insights on multispecies demographic dynamics, I designed the present study to focus on local and biogeographic influences on mortality and recruitment rates for tree populations in forest biomes throughout the Japanese archipelago.

Most populations exhibited mortality that fell within the 95% confidence intervals of a neutral model (i.e. the expectation of demographic stochasticity). However, there were also important determinants that make population dynamics to deviate from the neutral expectation. Interspecific niche differentiation was important to reduce the mortality rate, regardless of the local rarity or ubiquity of a species. Although intraspecific aggregation that caused density‐dependent mortality was only significant for locally abundant species, the degree of isolation from a species’ central or optimal range determined mortality only for locally rare species. These differences between rare and common species provide important empirical quantification of aspects of population dynamics that have been less accounted for in ecology and biogeography studies.

Synthesis. Unifying different theories such as those rooted in local‐scale community ecology and macro‐scale biogeography is important. At this juncture, this study emphasizes that disentangling the interactive roles of demographic stochasticity and determinism that operate at different scales would be a clue to advance the field of ecology both in theory and practice.
Effects of early‐season insect herbivory on subsequent pathogen infection and ant abundance on wild cotton (Gossypium hirsutum)
Authors: Abdala‐Roberts Luis , Pérez Niño Biiniza , Moreira Xoaquín , Parra‐Tabla Víctor , Grandi Luca , Glauser Gaétan , Benrey Betty , Turlings Ted C. J.
Published: January 2019

Plant‐induced defences play an important role in mediating interactions between plants, insects and pathogens. Yet, the plant traits underlying these effects, the extended consequences for higher trophic levels (i.e. predators), and the implications for plant growth and reproduction have received little attention.

Here, we asked whether simulated early insect leaf damage on wild cotton (Gossypium hirsutum) affected subsequent damage by insect leaf chewers and pathogenic fungi, as well as ant abundance. To address the mechanisms behind such effects, we measured plant defensive traits induced by early leaf damage to determine which inducible traits might determine the effects on plant‐associates. We also evaluated whether early damage influenced plant growth and flower production, and if such effects were mediated by subsequent insect herbivory or pathogen infection.

We show that simulated early leaf damage reduced damage by subsequent leaf‐chewing insects, increased plant fungal infections, but did not affect ant abundance. Leaf defensive traits (lignins and pubescence) were significantly induced by early damage and were negatively associated with insect herbivory and infection severity, but did not account for the effects of early leaf damage on either of these subsequent attackers. In addition, ant abundance was not associated with (or accounted for) subsequent herbivory or infection, suggesting they did not confer plant protection. Finally, early leaf damage negatively affected plant growth and flower production and analyses suggested that the effect on the latter was, at least partly, mediated by increased fungal infections.

Synthesis. Overall, these findings show that early herbivory determines the outcome of cotton interactions with subsequent attackers, and such effects have an impact on plant growth and flower output.
Contrasting altitudinal patterns of diversity between bumblebees and bumblebee‐visited flowers: Poverty of bumblebee diversity in a high mountain of Japan
Authors: Egawa Shin , Itino Takao
Published: January 2019

Range shifts of mountain organisms toward higher elevations in response to global warming may result in spatial mismatches between plants and their pollinators. Here, we aimed to examine whether bumblebee diversity decreases in a high‐altitude zone, and whether it parallels a decrease in the altitudinal diversity of bumblebee‐visited plants. We surveyed the alpha diversities of flower‐visiting bumblebees and bumblebee‐visited plants along an altitudinal gradient on a Japanese high mountain. Then, we examined whether the alpha diversities of bumblebees and bumblebee‐visited plants could be explained by altitude, or by other factors such as season, surveyed area and flower abundance. We found that a model including only altitude best explained bumblebee diversity, and that flower abundance and plant diversity had considerable value in explaining bumblebee diversity. In contrast, none of the studied factors explained plant diversity. Bumblebee diversity was minimal in the high‐altitude zone (1,900–2,600 m a.s.l.), where the only dominant bumblebee species, Bombus beaticola, visited many species of flowering plants. In contrast, five to seven bumblebee species were distributed in the low‐ (700–1,300 m a.s.l.) and middle‐ (1,300–1,900 m a.s.l.) altitude zones. These results show that plant–pollinator mutualism in high‐altitude zone of a Japanese mountain is asymmetric: many bee‐pollinated plants rely almost exclusively on one bumblebee species (B. beaticola) for pollination. Monitoring future changes in the distribution and abundance of B. beaticola is indispensable for the conservation of alpine plant in Japan.
Mitigation Strategies for the Reduction of 2‐ and 3‐MCPD Esters and Glycidyl Esters in the Vegetable Oil Processing Industry
Authors: Oey Sergio B. , van der Fels‐Klerx H.J. , Fogliano Vincenzo , van Leeuwen Stefan P.J.
Published: January 2019

The refining of vegetable oils leads to the formation of 2‐ and 3‐monochloropropane‐1,2‐diol esters (2‐ and 3‐MCPD‐E), and glycidyl esters (Gly‐E). A literature review was performed aiming to provide up‐to‐date knowledge on mitigation strategies during oil refining that can reduce the formation of these three processing contaminants. The review used the database Scopus and covered the period from 2009 to 2017. Most of the 18 papers dealt with palm oil and two papers with vegetable oil. Most studies focused on 3‐MCPD‐E, some on Gly‐E, and none on 2‐MCPD‐E. Water degumming was able to reduce the concentrations of 3‐MCPD‐E by 84% and Gly‐E by 26%. Neutralization of the oil reduced concentrations of 3‐MCPD‐E by 81% and Gly‐E by 84%. Bleaching with synthetic magnesium silicate reduced the 3‐MCPD‐E concentration by 67%. For the deodorization step, several mitigation strategies, such as double‐deodorization, the addition of various antioxidants, or a longer deodorization time, can reduce the formations of 3‐MCPD‐E by 82% and Gly‐E by 78%. Postrefining mitigation, including the use of absorbents, enzymes, or rebleaching of the oil, has also been reported to produce desirable contaminant reduction. Postrefining treatment with calcinated zeolite was able to reduce the 3‐MCPD‐E concentration by 19% and the Gly‐E concentration by 77%. Applying combined mitigation strategies to multiple steps of oil refining is likely crucial in order to adequately reduce levels of 3‐MCPD‐E and Gly‐E.
Dietary restriction and gonadal signaling differentially regulate post‐development quality control functions in Caenorhabditis elegans
Authors: Shpigel Nufar , Shemesh Netta , Kishner Mor , Ben‐Zvi Anat
Published: January 2019

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting in a sharp decline in folding capacity and reduced ability to cope with chronic and acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse and reshape the quality control network. Given that environmental conditions, such as food availability, impact reproductive success, we asked whether conditions of dietary restriction (DR) can also reverse the decline in quality control function at the transition to adulthood, and if so, whether gonadal signaling and dietary signaling remodel the quality control network in a similar or different manner. For this, we employed the eat‐2 genetic model and bacterial deprivation protocol. We found that animals under DR maintained heat shock response activation and high protein folding capacity during adulthood. However, while gonadal signaling required DAF‐16, DR‐associated rescue of quality control functions required the antagonistic transcription factor, PQM‐1. Bioinformatic analyses supported a role for DAF‐16 in acute stress responses and a role for PQM‐1 in cellular maintenance and chronic stress. Comparing the stress activation and folding capacities of dietary‐ and gonadal‐signaling mutant animals confirmed this prediction and demonstrated that each differentially impacts cellular quality control capabilities. These data suggest that the functional mode of cellular quality control networks can be differentially remodeled, affecting an organism's ability to respond to acute and chronic stresses during adulthood.
Histological and functional comparisons of four anatomical regions of porcine skin with human abdominal skin
Authors: Khiao In Maneenooch , Richardson Kenneth C. , Loewa Anna , Hedtrich Sarah , Kaessmeyer Sabine , Plendl Johanna
Published: January 2019

Because of the shortage of human skin for research purposes, porcine skin has been used as a model of human skin. The aim of this study was to identify the region of German Landrace pig skin that could be used as the best possible substitute for human abdominal skin. Porcine samples were collected from the ear, flank, back and caudal abdomen; human abdominal skin samples were excised during plastic surgery. Histological and ultrastructural assessments were carried out on the epidermis and dermis, with emphasis on the dermo‐epidermal interface length, dermo‐epidermal thickness ratio as well as densities of; hair follicles, arrector pili muscles, blood vessels and sweat glands. In the pig, the barrier function of the four anatomical regions was assessed. Results showed that both histologically and ultrastructurally, all four regions of porcine skin were similar to human skin. These include the shapes of keratinocytes, structure of cell contacts and presence of Weibel Palade bodies in endothelial cells. Other parameters such as the thickness of epidermis, the thickness of stratum basale, spinosum and granulosum and the number of cell layers in the stratum corneum were similar in human abdominal and in all four regions of porcine skin. However, there were also significant differences especially in the thickness of the stratum corneum, the dermo‐epidermal interface length and the blood vessel density.
Pharmacology of bisphosphonates
Authors: Cremers Serge , Drake Matthew T. , Ebetino F. Hal , Bilezikian John P. , Russell R. Graham G.
Published: January 2019

The biological effects of the bisphosphonates (BPs) as inhibitors of calcification and bone resorption were first described in the late 1960s. In the 50 years that have elapsed since then, the BPs have become the leading drugs for the treatment of skeletal disorders characterized by increased bone resorption, including Paget's disease of bone, bone metastases, multiple myeloma, osteoporosis and several childhood inherited disorders. The discovery and development of the BPs as a major class of drugs for the treatment of bone diseases is a paradigm for the successful journey from “bench to bedside and back again”. Several of the leading BPs achieved “blockbuster” status as branded drugs. However, these BPs have now come to the end of their patent life, making them highly affordable. The opportunity for new clinical applications for BPs also exists in other areas of medicine such as ageing, cardiovascular disease and radiation protection. Their use as inexpensive generic medicines is therefore likely to continue for many years to come. Fifty years of research into the pharmacology of bisphosphonates have led to a fairly good understanding about how these drugs work and how they can be used safely in patients with metabolic bone diseases. However, while we seemingly know much about these drugs, a number of key aspects related to BP distribution and action remain incompletely understood. This review summarizes the existing knowledge of the (pre)clinical and translational pharmacology of BPs, and highlights areas in which understanding is lacking.
Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®
Authors: Kandiah Nagaendran , Ong Paulus Anam , Yuda Turana , Ng Li‐Ling , Mamun Kaysar , Merchant Reshma Aziz , Chen Christopher , Dominguez Jacqueline , Marasigan Simeon , Ampil Encarnita , Nguyen Van Thong , Yusoff Suraya , Chan Yee Fai , Yong Fee Mann , Krairit Orapitchaya , Suthisisang Chuthamanee , Senanarong Vorapun , Ji Yong , Thukral Ramesh , Ihl Ralf
Published: January 2019

Background

The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer’s disease (AD).

Methods

To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence‐based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease.

Results

Key randomized trials and robust meta‐analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761®versus placebo in patients with mild‐to‐moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk‐benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta‐analyses have not supported this association.

Conclusions

The Expert Group foresee an important role for EGb 761®, used alone or as an add‐on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.
Keeping the Result in Sight and Mind: General Cognitive Principles and Language‐Specific Influences in the Perception and Memory of Resultative Events
Authors: Sakarias Maria , Flecken Monique
Published: January 2019

We study how people attend to and memorize endings of events that differ in the degree to which objects in them are affected by an action:Resultativeevents show objects that undergo a visually salient change in state during the course of the event (peeling a potato), andnon‐resultativeevents involve objects that undergo no, or only partial state change (stirring in a pan). We investigate general cognitive principles, and potential language‐specific influences, in verbal and nonverbal event encoding and memory, across two experiments with Dutch and Estonian participants. Estonian marks a viewer's perspective on an event's result obligatorily via grammatical case on direct object nouns: Objects undergoing a partial/full change in state in an event are marked with partitive/accusative case, respectively. Therefore, we hypothesized increased saliency of object states and event results in Estonian speakers, as compared to speakers of Dutch. Findings show (a) a general cognitive principle of attending carefully to endings of resultative events, implying cognitive saliency of object states in event processing; (b) a language‐specific boost on attention and memory of event results under verbal task demands in Estonian speakers. Results are discussed in relation to theories of event cognition, linguistic relativity, and thinking for speaking.
Lung clearance of inhaled aerosol of Tc‐99m‐methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender
Authors: Mohan Hosahalli K. , Livieratos Lefteris , Peters A. Michael
Published: January 2019

Tc‐99m‐methoxyisobutyl isonitrile (Tc‐99m‐MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc‐99m‐MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc‐99m‐MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc‐99m‐MIBI using a double‐headed gamma camera. The half‐time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin‐embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non‐smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2–3 in 8 and 1 in one (P<0·02). Mean clearance half‐time in smokers (142 ± 29 min; n = 17) was longer than in non‐smokers (91 ± 14 min; n = 18; P<0·0001). In non‐smokers, half‐times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half‐time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc‐99m‐MIBI. There is no significant gender difference in non‐smokers but ageing is associated with longer clearance half‐times.
Inequality of Opportunity in China's Labor Earnings: The Gender Dimension
Authors: Golley Jane , Zhou Yixiao , Wang Meiyan
Published: January 2019

This paper investigates the inequality of opportunity in China's labor earnings, defined as the component of inequality determined by personal circumstances that lie beyond the control of an individual, of which gender is one, as opposed to the component determined by personal efforts. Using the Survey of Women's Social Status in China (2010), we measure the share of inequality of opportunity in the total inequality of individual labor earnings for people aged 26–55 years, and separately for six birth cohorts and for female and male subsamples. Gender is revealed as the single most important circumstance determining nationwide individual labor earnings, with one's region of residence, father's occupation, father's education, birth cohort and holding rural or urban hukou also playing significant roles. A further investigation into the roles of circumstances and personal efforts (including education level, occupation, Communist Party membership, migration and marital status) confirms that circumstances play an alarmingly high role in shaping labor earnings distribution in China, and reveals notable gender differences that cannot be attributed to personal effort alone. These results provide the basis for recommending ways to improve gender equality of opportunity in the future.
Male pheromone composition depends on larval but not adult diet in Heliconius melpomene
Authors: Darragh Kathy , Byers Kelsey J. R. P. , Merrill Richard M. , McMillan W. Owen , Schulz Stefan , Jiggins Chris D.
Published: January 2019

1. Condition‐dependent traits can act as honest signals of mate quality, with fitter individuals being able to display preferred phenotypes. Nutrition is known to be an important determinant of individual condition, with diet known to affect many secondary sexual traits.

2. In Heliconius butterflies, male chemical signalling plays an important role in female mate choice. Potential male sex pheromone components have been identified previously, although it is unclear what information they convey to the female.

3. In the present study, the effect of diet on androconial and genital compound production is tested in male Heliconius melpomene rosina. To manipulate larval diet, larvae are reared on three different Passiflora host plants: Passiflora menispermifolia, the preferred host plant, Passiflora vitifolia and Passiflora platyloba. To manipulate adult diet, adult butterflies are reared with and without access to pollen, a key component of their diet.

4. No evidence is found to suggest that adult pollen consumption affects compound production in the first 10 days after eclosion. There is also a strong overlap in the chemical profiles of individuals reared on different larval host plants. The most abundant compounds produced by the butterflies do not differ between host plant groups. However, some compounds found in small amounts differ both qualitatively and quantitatively. Some of these compounds are predicted to be of plant origin and the others synthesised by the butterfly. Further electrophysiological and behavioural experiments will be needed to determine the biological significance of these differences.
Sustained atrial tachycardia in horses and treatment by transvenous electrical cardioversion
Authors: Van Steenkiste G. , De Clercq D. , Vera L. , Decloedt A. , van Loon G.
Published: January 2019

Background

Atrial tachycardia including focal atrial tachycardia and macroreentrant atrial tachycardia (atrial flutter), are occasionally found in horses. Diagnosis, treatment and follow‐up of these arrhythmias has been inadequately described.

Objectives

To describe the findings on surface electrocardiography (ECG), intra‐atrial electrogram recording and tissue Doppler imaging (TDI), the response to treatment by transvenous electrical cardioversion (TVEC), and TDI follow‐up, of sustained atrial tachycardia in horses.

Study design

Case series.

Methods

Records from horses with sustained atrial tachycardia treated by biphasic TVEC at Ghent University were reviewed. Horses with atrial fibrillation were not included.

Results

Seven horses with sustained atrial tachycardia were treated with TVEC. In six cases an exercise ECG was available and in 4 a 12‐lead ECG had been recorded. The mean bias between atrial cycle length measured from a right atrial intra‐atrial electrogram and from TDI ranged between −2 and 3 ms depending on the sampled region. All seven cases converted to sinus rhythm during the first TVEC procedure. TDI showed atrial contractile function recovery similar to cases that were treated for atrial fibrillation. One case developed atrial fibrillation 1 day after TVEC treatment, another case showed recurrence 8 years post conversion. The other five cases were still in sinus rhythm at 9 months – 5 years after TVEC.

Main limitations

Due to the small number of patients, data on recurrence and follow‐up of atrial recovery should be interpreted with caution. Since no invasive electrophysiology studies were performed, differentiation between focal atrial tachycardia and atrial flutter remains speculative.

Conclusions

Treatment of focal atrial tachycardia or atrial flutter by TVEC has a very high success rate. Tissue Doppler imaging allows noninvasive measurement of atrial cycle length and suggests reduced atrial function after cardioversion. Long‐term prognosis after cardioversion seemed similar compared to horses with atrial fibrillation, although early recurrence (<24 h) occurred in one horse.
The characteristics and spectrum of F9 mutations in Chinese sporadic haemophilia B pedigrees
Authors: Lu Yeling , Wu Xi , Dai Jing , Ding Qiulan , Wu Wenman , Wang Xuefeng
Published: January 2019

Introduction

Sporadic haemophilia B (HB) without obvious familial history poses challenges for genetic diagnosis and counselling.

Aim

To identify the F9 variants in sporadic HB patients and probe the origin of these de novo mutations.

Method

A total of 294 unrelated HB pedigrees sought genetic diagnosis were analysed in this single‐centre study. The F9 gene was analysed by direct sequencing, and AccuCopy technique was adopted to screen for gene copy number variations. Six short tandem repeats approximal or within F9 gene were applied for linkage analysis. Mosaicism of sequence variant was determined by ddNTP Primer Extension method.

Results

Sporadic HB patients constituted 36% (61/294) of cases enrolled in current study. The sporadic and familial HB patients shared similar spectrum of F9 variants, with single nucleotide substitution as predominant form of disease‐causing mutation and no mutation prone hotspot sites, including CpG dinucleotide sequences, had been identified. Majority of the mothers of sporadic HB patients were F9 mutation carriers (70%, 43/61), and most of them (95%, 41/43) had the inherited bleeding trait traced back to maternal grandfathers. Although most de novo mutations occur in germ cells, 2 maternal grandfathers, who had somatic mosaic mutations of F9, were also revealed to be the source of genetic variations identified in patients. In our cohort, FIX inhibitor incidence was 1%, developed only in patients carrying null mutations.

Conclusion

The diversity of F9 genetic variants and possible mosaicism of de novo mutation demand extensive study and more cautious in genetic counselling of sporadic HB.