bluuebunny/crossref_metadata_2025 huggingface dataset:
The Case of Synthroid (A): Marketing a Drug Coming Off Patent
Authors: Tybout Alice M. , Hennessy Julie , Fahey Natalie , Snyder Charlotte
Published: March 2017

The case tells the story of Synthroid from its development in 1958 as the first synthetic thyroxine molecule to its competition against generic equivalents in 2004. The case introduces students to the pharmaceutical industry, its practices, and some of the complexities of pricing and drug choice, with drug manufacturers, insurance companies, physicians, pharmacists, and patients all playing a role. It also provides a primer on hypothyroidism, its symptoms, and its treatment.

Because Synthroid was developed and introduced before FDA regulations and drug standards of identity were fully established, it was difficult for competitors to get their drugs certified as identical to Synthroid. Through a series of efforts with physicians, especially endocrinologists, Synthroid's owners were able to maintain the perception for forty-six years that Synthroid was uniquely effective. In 2004, however, the FDA declared several competitive products to be bioequivalent to Synthroid, which posed a significant challenge to its owner, Abbott Laboratories. Students are challenged to consider options to maintain the drug's unit volume, revenue, and/or profit in these difficult circumstances.

The case is written in two parts. The (A) case provides background on the history of the drug, the pharmaceutical industry and its marketing practices, and hypothyroidism and its treatment, and it concludes in 2004 as Abbott's marketers face the impending challenge of defending the Synthroid business against generic competition. The (B) case describes what Abbott actually did to maintain its share in the United States and outlines its strategy in India, a market without patent protection for pharmaceuticals.

After analyzing the case students should be able to:

Describe strategies that branded competitors can use to defend their business from lower-priced competition

Understand the basics of pharmaceutical marketing and pricing, including the global challenge of defending branded drugs against generic equivalents

Discuss ethical issues in the marketing of high-margin branded products that have lower-priced alternatives, especially in the healthcare industry
The U.S. Airline Industry in 1995
Authors: Dana James D. , Schmitt David A.
Published: March 2017

Provides an overview of the domestic airline industry. Offers details on industry structure and performance necessary for basic industry analysis (or five forces analysis). Also emphasizes cost and benefit drivers, especially hub-and-spoke vs. point-to-point service and sources of differentiation.
The effects of platform as a technology standard on platform-based repurchases
Authors: Kim Hongbum , Shin Dong-Hee
Published: March 2017

Purpose

Using the critical incident technique, this study aims to identify the attributes of a platform as a technology standard and to investigate their effects on platform-based repurchases.

Design/methodology/approach

Smartphone users’ personal experiences and levels of satisfaction or dissatisfaction were collected and categorized into technology standard attributes to estimate those factors affecting consumers’ intention to purchase platform-based products and services.

Findings

The study findings show the importance of understanding which attributes are important to promoting future platform-based purchases and maximizing positive experiences when using platform-based products and services.

Research limitations/implications

Given the effect of the platform vendor on repurchases, and that various lock-in strategies are being implemented, firms attempting to be leaders in the information and communications technology (ICT) ecosystem should seek appropriate strategies to lock-in their installed base.

Originality/value

Including discussions on the competition in the ICT ecosystem, this study also provides some policy suggestions and contributions for applicability to an integrated approach.
A reconciliation proposal of demand-driven growth models in open economies
Authors: Ribeiro Rafael Saulo Marques , McCombie John S.L. , Tadeu Lima Gilberto
Published: March 2017

Purpose

The purpose of this paper is to contribute to the literature on demand-driven Keynesian growth in open economies by developing a formal model that combines Dixon and Thirlwall’s (1975) export-led growth model and Thirlwall’s (1979) balance-of-payments constrained growth model into a more general specification. Then, based on the model developed in this paper, the authors analyse more broadly some important issues concerning the net impact of currency depreciation on the short-run growth.

Design/methodology/approach

The authors build upon Dixon and Thirlwall’s (1975) export-led growth model and Thirlwall’s (1979) balance-of-payments constrained growth model in order to develop the theoretical framework. The authors also run numerical simulations to illustrate the net impact of devaluation on the short-run growth rate in different scenarios.

Findings

The authors demonstrate that the net impact of currency devaluation on growth can go either way, depending on some structural conditions such as the average share of imported intermediate inputs in prime costs of domestic firms and the institutional capacity of trade unions to set nominal wages through the bargaining process. The model also shows that the effectiveness of a competitive real exchange rate to promote growth is higher in countries where the share of labour in domestic income is also higher.

Research limitations/implications

This paper provides a coherent formal starting-point for further theoretical developments on the interrelatedness between currency devaluation, income distribution and growth. These findings provide empirically testable hypothesis for future research.

Originality/value

The present study proposes an alternative formal solution for the theoretical problem of imposing a balance-of-payments constraint on the process of cumulative causation often incorporated in Kaldorian growth models. In terms of policy, the framework sheds further light on the relevance of income distribution and the labour market institutional framework for the dynamics of the exchange rate pass-through mechanism and allows us to map out related conditions under which currency devaluation can promote growth.
Sustainable apparel design strategies regenerated from traditional costumes of the Chosun Dynasty
Authors: Min Seoha , Koo Helen
Published: March 2017

Purpose

This study aims to provide insights to designers for seeking innovative ways to design sustainable clothes and appeal to consumers by enhancing sustainability.

Design/methodology/approach

To achieve the research purpose, the researchers went through a design process and designed three prototypes. The experts’ evaluation on the prototypes was positive.

Findings

Various design strategies derived from the Korean traditional costume were explored. Based on the strategies, three prototypes were developed, and the design experts’ evaluation on the prototypes was positive.

Originality/value

The research has implications as follows. The sustainable design process and methods used in this research for developing designs inspired from cultural costumes will provide insights to designers who want to create sustainable garments inspired by a certain culture. In addition, the design and sustainable design strategies, derived from the Chosun Dynasty, will guide apparel designers to create sustainable designs and broaden their perspectives. Furthermore, the research will provide guidance to following researchers who are interested in the topic of sustainability in apparel design. The researchers explored sustainable design strategies from the Korean culture, applied them in their design process and evaluated the design outcomes. By doing so, merits and limitations of the design strategies were more clearly understood.
Oil and Regional Development in Chad: Assessment of the Impact of the Doba Oil Project on Poverty in the Host Region
Authors: Aristide Mabali , Moundigbaye Mantobaye
Published: March 2017

In 1999, the Chad Government passed Law No. 001/PR/1999, establishing rules for allocating and managing the expected oil income from the Doba Oil project. The oil producing region's share amounts to 5 per cent of royalties, in addition to other benefits related to its status as an oil producing region, in order to mitigate negative effects from the oil project. This paper assesses the poverty profile in the Logone Oriental region, by combining a double difference estimator with propensity score matching methods. Data from two panels of the Survey on Consumption and the Informal Sector in Chad carried out in 2003 and 2011 show that monetary poverty increased in the oil producing region compared to the control regions. No evidence was found that non‐monetary poverty decreased in the oil producing region, as large investments in social infrastructure in the region might have suggested. In addition, it was found that household expenditure for temptation goods increased in this region compared with other regions. Finally, spillover effects were observed — the oil producing region's neighboring regions are more likely to experience poverty. These results cast doubt on the effectiveness of the law and of its replication for newly discovered oil fields.
Clinical and computed tomography findings in Chinese lung cancer patients with HIV infection: A multi‐center study
Authors: Cheng Zenghui , Shan Fei , Liu Jinxin , Shi Yuxin , Zhang Zhiyong , Wu Guowei
Published: March 2017

Background

The study was conducted to investigate clinical and computed tomography (CT) features in Chinese lung cancer patients with human immunodeficiency virus (HIV).

Methods

Forty consecutive lung cancer patients with HIV were included. Clinical data were collected, and CT features were reviewed and measured. The factors associated with stages of cancer and the CT features with opportunistic pulmonary infections (OPIs) were also analyzed.

Results

Thirty‐four of the patients were men (85%), and the mean age was 57.5 years. The mean CD4 count was 288 cells/μL, and 23 patients received highly active antiretroviral therapy. OPIs were common (50%). The major histological type (85%) was non‐small cell lung cancer (NSCLC), and 15 NSCLC patients (44%) were in stages IIIb and IV. NSCLC patients with an OPI were more common in the advanced stages compared with those without an OPI (P = 0.04). There were no significant differences in advanced and non‐advanced stages in terms of CD4 level, highly active antiretroviral therapy, and smoking (P = 0.31, P = 1.00; P = 0.49, respectively). The average size of tumors was 4.5 cm. Irregularly shaped or larger sized tumors were associated with OPIs (P = 0.03, P = 0.04, respectively).

Conclusions

The persistence of locally irregular and large lesions in middle‐aged men with HIV and a history of OPIs should be an alert for lung cancer, and clinical management is needed.
Preconception TSH and pregnancy outcomes: a population‐based cohort study in 184 611 women
Authors: Chen Shi , Zhou Xiang , Zhu Huijuan , Yang Hongbo , Gong Fengying , Wang Linjie , Zhang Man , Jiang Yu , Yan Chengsheng , Li Jianqiang , Wang Qing , Zhang Shikun , Pan Hui
Published: March 2017

Background

Whether subclinical hypothyroidism adversely impacts pregnancy outcomes is inconclusive, and limited data are available on the optimal TSH range in women planning pregnancy.

Objective

To investigate the association between maternal preconception TSH levels and pregnancy outcomes.

Design

Population‐based cohort study.

Methods

From 2010 to 2012, the free National Pre‐pregnancy Checkups Project recruited 248 501 pairs of volunteer couples across China, of which 184 611 women, who subsequently became pregnant, were studied. Maternal TSH was measured within 6 months prior to conception. Participants were grouped according to TSH: 0·48–2·49 mIU/l (n = 133 232, 72%), 2·50–4·28 mIU/l (n = 44 239, 24%) and 4·29–10·0 mIU/l (n = 7140, 4%). Multivariable logistic regression models were used to study the association between TSH and pregnancy outcomes.

Main outcomes

Pregnancy loss, gestational age (GA), delivery modes and birthweight.

Results

The overall incidence of adverse pregnancy outcomes was 28·6%. Compared with TSH 0·48–2·50 mIU/l, TSH 2·50–4·29 mIU/l was associated with spontaneous abortion [aOR: 1·10, 95% confidence interval (CI): 1·03–1·18], preterm birth (aOR: 1·09, 95% CI: 1·04–1·15) and operative vaginal delivery (aOR: 1·15, 95% CI: 1·09–1·21), while TSH 4·29–10 mIU/l was correlated with spontaneous abortion (aOR: 1·15, 95% CI: 1·10–1·22), stillbirth (aOR: 1·58, 95% CI: 1·10–2·28), preterm birth (aOR: 1·20, 95% CI: 1·08–1·34), caesarean section (aOR: 1·15, 95% CI: 1·10–1·22) and large for gestational age (LGA) infants (aOR: 1·12, 95% CI: 1·04–1·21).

Conclusion

Preconception TSH elevation was associated with increased risk of adverse pregnancy outcomes, even within the normal nonpregnant range.
Effects of national forest‐management regimes on unprotected forests of the Himalaya
Authors: Brandt Jodi S. , Allendorf Teri , Radeloff Volker , Brooks Jeremy
Published: March 2017

Globally, deforestation continues, and although protected areas effectively protect forests, the majority of forests are not in protected areas. Thus, how effective are different management regimes to avoid deforestation in non‐protected forests? We sought to assess the effectiveness of different national forest‐management regimes to safeguard forests outside protected areas. We compared 2000–2014 deforestation rates across the temperate forests of 5 countries in the Himalaya (Bhutan, Nepal, China, India, and Myanmar) of which 13% are protected. We reviewed the literature to characterize forest management regimes in each country and conducted a quasi‐experimental analysis to measure differences in deforestation of unprotected forests among countries and states in India. Countries varied in both overarching forest‐management goals and specific tenure arrangements and policies for unprotected forests, from policies emphasizing economic development to those focused on forest conservation. Deforestation rates differed up to 1.4% between countries, even after accounting for local determinants of deforestation, such as human population density, market access, and topography. The highest deforestation rates were associated with forest policies aimed at maximizing profits and unstable tenure regimes. Deforestation in national forest‐management regimes that emphasized conservation and community management were relatively low. In India results were consistent with the national‐level results. We interpreted our results in the context of the broader literature on decentralized, community‐based natural resource management, and our findings emphasize that the type and quality of community‐based forestry programs and the degree to which they are oriented toward sustainable use rather than economic development are important for forest protection. Our cross‐national results are consistent with results from site‐ and regional‐scale studies that show forest‐management regimes that ensure stable land tenure and integrate local‐livelihood benefits with forest conservation result in the best forest outcomes.
Influence of continuous use of a vacuum‐forming machine for mouthguard thickness after thermoforming
Authors: Takahashi Mutsumi , Araie Yoshiaki , Satoh Yoshihide , Iwasaki Shin‐ichi
Published: March 2017

Background/Aims

Mouthguards can reduce the risk of sports‐related injuries such as tooth fracture or avulsion, but the sheet material and thickness have a large effect on their efficacy and safety. The aim of this study was to investigate the effect of the continuous use of a vacuum‐forming machine on mouthguard thickness.

Materials and Methods

Ethylene vinyl acetate sheets and olefin copolymer sheets were used for thermoforming with a vacuum‐forming machine. The working model was trimmed to a height of 23 mm at the maxillary central incisor and 20 mm at maxillary first molar. During molding, the model was placed at the center of the vacuum unit. Three molding conditions were investigated (i) molding was carried out after the sag at the center of the softened sheet was 15 mm below the clamp (control); (ii) sheet heating started 5 minutes after the control, and molding in the same way as the control (AF5); and (iii) sheet heating started 10 minutes after the control, and molding in the same way as the control (AF10). Under each condition, vacuum forming was conducted for 30 seconds. Sheet thickness after fabrication was determined for the incisal edge, labial surface, cusp, and buccal surface using a special caliper accurate to 0.1 mm. The differences of the molding conditions on the thickness in each sheet material were analyzed by one‐way analysis of variance and Bonferroni's multiple comparison tests.

Results

For both sheet materials, significant differences between the control and AF5 were observed at all measurement points (P<.01), but not between the control and AF10. Compared with the control, AF5 was thinner and AF10 was a similar thickness.

Conclusion

The continuous use of a vacuum‐forming machine led to a reduction in the thickness of the mouthguard. Intervals of 10 minutes are necessary to achieve consistent molding.
Maxillofacial trauma patterns associated with external auditory canal fractures: Cone beam computed tomography analysis
Authors: Ali Ibrahim K. , Sansare Kaustubh , Karjodkar Freny R. , Salve Prashant , Vanga Kavita , Pawar Ajinkya M.
Published: March 2017

Background/Aims

There is a paucity of literature on external auditory canal (EAC) fractures secondary to maxillofacial trauma, with most of the literature on EAC fractures consisting of isolated case reports. To the authors’ best knowledge, this is the first study to use cone beam computed tomography to evaluate the EAC region. The aim of this study was to assess the prevalence of external auditory canal (EAC) fracture following maxillofacial trauma and to evaluate the association between EAC fracture and other maxillofacial fractures and the region of trauma.

Materials and Methods

One hundred patients were prospectively evaluated over 6 months from February to August 2016. The patients were referred for CBCT regarding temporomandibular joint or condylar fractures following maxillofacial trauma. Two observers (both experienced radiologists) assessed the EAC and associated fractures in the maxillofacial region.

Results

External auditory canal (EAC) fracture was confirmed in 32% of the patients. Of the EAC fractures, 68.75% and 31.25% were associated with mandibular fractures and non‐mandibular fractures, respectively. Of the EAC fractures, 68.75% were single fractures and 31.25% of patients had multiple comminuted fractures. Significant association was observed on cross‐tabulation of the fractured region and region of trauma with the presence of EAC fracture using chi‐square test.

Conclusion

External auditory canal (EAC) fracture is associated with maxillofacial fractures with increased incidence in mandibular fractures compared to non‐mandibular fractures.
Modulating risky decision‐making in Parkinson's disease by transcranial direct current stimulation
Authors: Benussi A. , Alberici A. , Cantoni V. , Manenti R. , Brambilla M. , Dell'Era V. , Gazzina S. , Manes M. , Cristillo V. , Padovani A. , Cotelli M. , Borroni B.
Published: March 2017

Background and purpose

Performance on gambling tasks in Parkinson's disease (PD) is of particular interest, as pathological gambling is often associated with dopamine replacement therapy in these patients. We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) in modulating gambling behaviour in PD.

Methods

We assessed the effects of cathodal tDCS over the right DLPFC during the Iowa Gambling Task in 20 patients with PD, compared with sham stimulation. We then conducted a second experimental design, assessing the effects of anodal tDCS over the right DLPFC.

Results

We observed that cathodal tDCS over the right DLPFC increased Iowa Gambling Task scores compared with sham stimulation. In the second experimental design, we did not find significant differences between anodal and sham tDCS.

Conclusions

Cathodal tDCS over the right DLPFC possibly reduces the pathological overdrive in frontostriatal networks in patients with PD on dopaminergic medication, thus modulating impulsive and risky decision‐making.
A Permanent Multilevel Monitoring and Sampling System in the Coastal Groundwater Mixing Zones
Authors: Luo Xin , Kwok King Lun , Liu Yi , Jiao Jimmy
Published: March 2017

To study the spatial and temporal variability of water dynamics and chemical reactions within the coastal groundwater mixing zones (CGMZs), high‐resolution periodical and spatial groundwater sampling within CGMZs is needed. However, current samplers and sampling systems may require heavy driving machines to install. There is also possible contamination from the metal materials for current samplers and sampling systems. Here, a permanent multilevel sampling system is designed to sample coastal groundwater within CGMZs. This cost‐effective system consists of metal‐free materials and can be installed easily. The system is tested in Po Sam Pai and Tingkok, Tolo Harbor and Hong Kong. Major ions, nutrients, stable isotopes and radium and radon isotopes were analyzed and the data provided scientific information to study the fresh‐saltwater interface fluctuations, and temporal variations and spatial heterogeneity of geochemical processes occurred within CGMZs. The reliable spatial and temporal data from the sampling system demonstrate that the system functions well and can provide scientific data for coastal aquifer studies.
HFE mutations and iron in hemodialysis patients
Authors: Valenti Luca , Pelusi Serena
Published: March 2017

In chronic hemodialysis patients, a disruption in iron metabolism ranging from absolute to functional deficiency, with compartmentalization of this metal into macrophages, is often observed. Chronic inflammation indeed often causes an upregulation of the iron hormone hepcidin, thereby reducing iron absorption and availability to the erythron. We systematically reviewed the literature on the role of genetic risk factors on iron metabolism in hemodialysis. In this setting, mutations in the HFE gene of hereditary hemochromatosis may confer an adaptive benefit by decreasing hepcidin release, thus improving iron availability to erythropoiesis, anemia control, and the response to erythropoiesis stimulating agents and iron itself, and reducing the side effects of these therapies. The HFE protein together with Transferrin receptor‐2 may also have a direct role on erythroid differentiation and iron uptake in erythroid cells. In addition, other genetic determinants of iron status, such as variants in Matriptase‐2 (TMPRSS6), have been shown to influence iron metabolism in chronic hemodialysis patients, most likely acting through hepcidin regulation. Although data must be confirmed in larger prospective studies, this favorable shift in iron metabolism balance possibly results in reduced mortality, in particular because of cardiovascular and infective diseases. Further genetic studies may offer a valuable tool to test these hypotheses and guide personalized clinical management and the research of new therapies.
Hydrogen peroxide reduces heat‐induced yield losses in cotton (Gossypium hirsutum L.) by protecting cellular membrane damage
Authors: Sarwar M. , Saleem M. F. , Najeeb U. , Shakeel A. , Ali S. , Bilal M. F.
Published: March 2017

We investigated the effect of various growth substances such as hydrogen peroxide, salicylic acid (SA), moringa leaf‐extract (MLE) and ascorbic acid (ASA) on leaf physiology and seed cotton yield (SCY) of heat‐stressed cotton. Cotton plants were exposed to elevated temperatures at three reproductive stages, either by staggering planting time in the field or by increasing growth cabinet temperatures (38/24°C and 45/30°C) in glasshouse. Elevated temperature at any reproductive phase significantly damaged cellular membrane and reduced SCY. Plants exposed to 38/24°C and 45/30°C in glasshouse produced 63% and 22% lower SCY, respectively, compared with plants under optimal temperature ((32/20°C). In response to high temperature, cotton plants up‐regulated activities of anti‐oxidative enzymes e.g. peroxidase and ascorbic acid. However, this defensive system could not protect cellular membrane of stressed plants from extreme temperature (38 and 45°C). In contrast, growth substances such as H2O2, ASA and MLE significantly increased anti‐oxidative enzymes activity to an extent, which reduced heat‐induced damage to cellular membrane. No significant effect of any regulator was observed on SCY under optimum temperatures; although H2O2, MLE and ASA significantly increased SCY of heat‐stressed cotton. Hydrogen peroxide increased SCY of April and May thermal regimes crops by 16% (averaged across both sowing dates) under field, while it caused 14% and 20% increase in SCY of plants exposed to sub (38/24°C) and supra optimal (45/30°C) thermal regimes under glasshouse. We concluded that growth regulators, specifically, H2O2 can protect cotton crops from heat‐induced cellular membrane damage by up‐regulating antioxidant defense system.
A New Formula for Estimating the True QT Interval in Left Bundle Branch Block
Authors: WANG BINHAO , ZHANG LI , CONG PEIXIN , CHU HUIMIN , LIU YING , LIU JINQIU , SURKIS WILLIAM , XIA YUNLONG
Published: March 2017

A New QT Formula for LBBB

Introduction

QT prolongation is an independent risk factor for cardiac mortality. Left bundle branch block (LBBB) is more common in patients as they age. Widening of the QRS in LBBB causes false QT prolongation and thus makes true QT assessment difficult. We aimed to develop a simple formula to achieve a good estimate of the QT interval in the presence of LBBB.

Methods and Results

To determine the effect of QRS duration on the QT interval, QRS and QT were measured in sinus rhythm and during right ventricular apical pacing in 62 patients (age 55 ± 11 years, 60% male) undergoing electrophysiology studies. A QT formula for LBBB (QT‐LBBB) was derived based on the effect of increased QRSLBBB on QTLBBB. The predictive accuracy of the QT‐LBBB formula was then tested in 22 patients (age 66 ± 13 years, 64% male) with intermittent LBBB with comparisons to prior QT formulae and JT index. On average, the net increase in QRSLBBB constituted 92% of the net increase in QTLBBB. A new formula, QT‐LBBB = QTLBBB – (0.86 * QRSLBBB – 71), which takes the net increase in QRSLBBB into account, best predicted the QT interval with heart rate corrected QTc in the test set of LBBB ECGs when compared to the baseline value and prior formulae.

Conclusion

The QT‐LBBB formula developed in this study best estimates the true QT interval in the presence of LBBB. It is simple and therefore can be easily utilized in clinical practice.
The Redistributive Impact of Restrictive Measures on EU Members: Winners and Losers from Imposing Sanctions on Russia
Authors: Giumelli Francesco
Published: March 2017

EU sanctions on Russia created concerns among its members. It is well known that sanctions impose a cost on their targets as well as on the senders, as lamented by European governments, but the costs of EU sanctions on its members have not been fully explored. This article intends to fill this gap by looking at the cost of EU sanctions on Russia. Who is bearing the cost among EU countries? This article argues that sanctions had a redistributive impact across the EU. Whereas exports fell for all countries, with Germany, Italy and Finland in the leading positions, the article shows that there are economic sectors that increased their exports to Russia after the imposition of sanctions, which occurred particularly in countries as Greece, Sweden, Luxembourg and Bulgaria. This conclusion is reached by looking at the export flows from individual EU member states divided by SITC sectors to Russia.
Acetylglutamate kinase is required for both gametophyte function and embryo development in Arabidopsis thaliana
Authors: Huang Jie , Chen Dan , Yan Hailong , Xie Fei , Yu Ying , Zhang Liyao , Sun Mengxiang , Peng Xiongbo
Published: March 2017

The specific functions of the genes encoding arginine biosynthesis enzymes in plants are not well characterized. We report the isolation and characterization of Arabidopsis thaliana N‐acetylglutamate kinase (NAGK), which catalyzes the second step of arginine biosynthesis. NAGK is a plastid‐localized protein and is expressed during most developmental processes in Arabidopsis. Heterologous expression of the Arabidopsis NAGK gene in a NAGK‐deficient Escherichia coli strain fully restores bacterial growth on arginine‐deficient medium. nagk mutant pollen tubes grow more slowly than wild type pollen tubes and the phenotype is restored by either specifically through complementation by NAGK in pollen, or exogenous supplementation of arginine. nagk female gametophytes are defective in micropylar pollen tube guidance due to the fact that female gametophyte cell fate specification was specifically affected. Expression of NAGK in synergid cells rescues the defect of nagk female gametophytes. Loss‐of‐function of NAGK results in Arabidopsis embryos not developing beyond the four‐celled embryo stage. The embryo‐defective phenotype in nagk/NAGK plants cannot be rescued by watering nagk/NAGK plants with arginine or ornithine supplementation. In conclusion, our results reveal a novel role of NAGK and arginine in regulating gametophyte function and embryo development, and provide valuable insights into arginine transport during embryo development.
Calmodulin kinases: essential regulators in health and disease
Authors: Takemoto‐Kimura Sayaka , Suzuki Kanzo , Horigane Shin‐ichiro , Kamijo Satoshi , Inoue Masatoshi , Sakamoto Masayuki , Fujii Hajime , Bito Haruhiko
Published: March 2017

Neuronal activity induces intracellular Ca2+ increase, which triggers activation of a series of Ca2+‐dependent signaling cascades. Among these, the multifunctional Ca2+/calmodulin‐dependent protein kinases (CaMKs, or calmodulin kinases) play key roles in neuronal transmission, synaptic plasticity, circuit development and cognition. The most investigated CaMKs for these roles in neuronal functions are CaMKI, CaMKII, CaMKIV and we will shed light on these neuronal CaMKs’ functions in this review. Catalytically active members of CaMKs currently are CaMKI, CaMKII, CaMKIV and CaMKK. Although they all necessitate the binding of Ca2+ and calmodulin complex (Ca2+/CaM) for releasing autoinhibition, each member of CaMK has distinct activation mechanisms—autophosphorylation mediated autonomy of multimeric CaMKII and CaMKK‐dependent phosphoswitch‐induced activation of CaMKI or CaMKIV. Furthermore, each CaMK shows distinct subcellular localization that underlies specific compartmentalized function in each activated neuron. In this review, we first summarize these molecular characteristics of each CaMK as to regulation and subcellular localization, and then describe each biological function. In the last section, we also focus on the emerging role of CaMKs in pathophysiological conditions by introducing the recent studies, especially focusing on drug addiction and depression, and discuss how dysfunctional CaMKs may contribute to the pathology of the neuropsychological disorders.

This article is part of the mini review series “60th Anniversary of the Japanese Society for Neurochemistry”.

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Assessment of the efficacy and safety of single platelet‐rich plasma injection on different types and grades of facial wrinkles
Authors: Elnehrawy Naema Y , Ibrahim Zeinab A , Eltoukhy Azza M , Nagy Hala M
Published: March 2017

Background

Platelet‐rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration.

Aim of the study

To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation.

Patients and methods

A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale.

Results

The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability.

Conclusion

Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs.
Ten pearls every dermatologist should know about the appropriate use of relaxers
Authors: Richardson Vanessa , Agidi Ada T , Eaddy Erica R , Davis Loretta S
Published: March 2017

Chemical relaxers are products marketed to straighten the hair and have been principally used by African Americans since the early twentieth century. They contain alkaline agents that break and reform hydrogen and disulfide bonds, leaving hair permanently straightened. Relaxers cause loss of tensile strength and increased fragility of the hair shaft that lead to increased risk of hair breakage and thinning. When used improperly, they can also cause local irritant contact dermatitis and chemical burns to the scalp and hairline that can potentially lead to a scarring alopecia. After interviewing several cosmetology educators in the field and reviewing the literature, we generated a list of ten pearls that all dermatologists should know about relaxers to provide professional guidance to their patients.
Overweight or obesity in children aged 0 to 6 and the risk of adult metabolic syndrome: A systematic review and meta‐analysis
Authors: Kim Jieun , Lee Insook , Lim Sungwon
Published: March 2017

Aims and objectives

To identify an association between overweight or obesity in early childhood and metabolic syndrome in adults.

Background

Early childhood overweight or obesity is important because it can predict metabolic syndrome in adulthood. A longer period of overweight or obesity leads to the accumulation of more risk factors. However, there are insufficient and inconsistent studies on this issue.

Design

A systematic review and meta‐analysis.

Methods

We followed the Meta‐Analysis of Observational Studies in Epidemiology guideline, MEDLINE, EMBASE, Cochrane library and CINAHL electronic databases as well as reference lists of included studies were searched, without published date restriction. We used the Newcastle‐Ottawa Scale to assess the quality of the observational studies in the systematic review, and the meta‐analysis was performed using random‐effects models.

Results

All of the included studies were published from 2008–2014, and the participants of this study were only Asians or Europeans. A total of 12 results from five studies were included in the meta‐analysis. Overweight or obesity in early childhood was associated with a higher risk of adult metabolic syndrome compared with the controls. When confirmed in each age group (at birth, 0–2 and 2–6 years), there was a statistically significant difference before and after the age of 2 years. As a result of the meta‐regression, when the age of the children increased, the effect size of adult metabolic syndrome for overweight or obesity also increased.

Conclusions

The results confirm that the aetiology of metabolic syndrome includes long‐term impacts from the early stage of life and indicate that early intervention for overweight or obesity is needed. Relevance to clinical practice: these findings could help community and clinical health nurses recognize the risk of overweight or obesity in early life, and provide evidence to develop and implement the preventive intervention for early childhood.
Health‐related quality of life and satisfaction with case management in cancer survivors
Authors: Hsu Ya‐Hui , Chai Hsiu‐Ying , Lin Yu‐Fen , Wang Chao‐Hui , Chen Shu‐Ching
Published: March 2017

Aims and objectives

To (i) investigate the characteristics of health‐related quality of life and satisfaction with case management and (ii) to identify factors associated with health‐related quality of life in cancer survivors.

Background

The level of health‐related quality of life can reflect treatment efficacy and satisfaction with cancer care.

Design

A cross‐sectional study design was adopted.

Methods

Subjects from the outpatient setting of a cancer centre in northern Taiwan were recruited by consecutive sampling. A set of questionnaires were employed, including a background information form, case management service satisfaction survey (CMSS) and The European Quality of Life Scale (EQ‐5D). Descriptive statistics were used to examine levels of health‐related quality of life and satisfaction with case management. Pearson's correlation was used to identify relationships between treatment characteristics, satisfaction with case management and health‐related quality of life. Multiple stepwise regression was used to identify factors associated with health‐related quality of life.

Results

A total of 252 cancer patients were recruited. The three lowest scores for items of health‐related quality of life were mobility, self‐care and usual activities. Cancer survivors with higher mobility, less pain and discomfort, and lower anxiety and depression were more likely to have better health‐related quality of life.

Conclusion

Mobility, pain and discomfort, and anxiety and depression are important predictive factors of high health‐related quality of life in cancer survivors.

Relevance to clinical practice

In clinical care, patients’ physical mobility, pain and discomfort, and anxiety and depression are important indicators of health‐related quality of life. Case managers should include self‐care and symptom management into survivorship care plans to improve health‐related quality of life during survival after treatment concludes.
On the Failure (Success) of the Markets for Longevity Risk Transfer
Authors: MacMinn Richard , Brockett Patrick
Published: March 2017

ABSTRACT

Longevity risk is the chance that people will live longer than expected. That potential increase in life expectancy exposes insurers and pension funds to the risk of not having sufficient funds to pay a longer stream of annuity benefits than promised. Longevity bonds and forwards provide insurers and pension funds with financial market instruments designed to hedge the longevity risk that these organization face. The European Investment Bank and World Bank have both discussed longevity bond issues, but those issues have failed due to insufficient demand. Forward contracts have also been created, but that market remains dormant. The extant literature suggests that these failures may be due to design or pricing problems. In this article the analysis shows that the market failure is instead due to a moral hazard problem.
Preparation, pharmacokinetics and tumour-suppressive activity of berberine liposomes
Authors: Wang Xinghui , Wang Qiong , Liu Zhihui , Zheng Xiao
Published: March 2017

Objectives

Berberine (BBR) has shown promising antitumour effects in vitro. However, intravenous administration of BBR solution is complicated by lethal adverse cardiovascular effects. The aim of this study was to prepare common and polyethylene glycol (PEG)-modified long-circulating BBR liposomes and evaluate their efficacy and safety as potential antitumour agents.

Methods

Physiochemical properties of common and long-circulating BBR liposomes were characterized including particle size, Zeta potential and thermal stability. Pharmacokinetic and tissue distribution study of liposomal BBR was performed in rats and tumour-bearing nude mice, respectively. Antitumour efficacy and safety were observed in SGC-7901 tumour-xenografted mice.

Key findings

Berberine liposomes showed homogenous morphology, storage stability and sustained-releasing behaviour in vitro. BBR liposomes led to significantly increased circulation retention of BBR in comparison with BBR solution. In tumour-bearing mice, BBR liposomes selectively increased BBR concentrations in the liver, spleen, lung and tumour, while conferred lower distribution to the heart and kidney. Importantly, chronic administration of BBR liposomes proved effective and safe in suppressing the tumour growth in nude mice, especially the PEG-modified long-circulating liposomes.

Conclusion

Our study suggested that BBR liposomes may provide a safe form of intravenous drug therapy for strengthening the antitumour effects of BBR.
Process Innovation: Open Innovation and the Moderating Role of the Motivation to Achieve Legitimacy
Authors: Tsinopoulos Christos , Sousa Carlos M. P. , Yan Ji
Published: March 2017

Global competition has increased the pressure for firms to develop new and efficient processes in ways that are perceived to be legitimate. At the same time, there has been a realization that engaging with open innovation can improve competitiveness. Our study aims to address two research questions: (a) How does engaging with open innovation support an organization's process innovation? and (b) How does the motivation to achieve legitimacy affect the relationship between engaging with open innovation and process innovation? We use arguments from the resource‐based view to explain how open innovation influences an organization's likelihood of introducing new processes. We then use arguments from institutional theory to explain how the motivation to achieve legitimacy moderates this relationship. We test our conceptual model using data from the European Community Innovation Survey administered by the U.K. government. Our findings and theoretical development support the notion that engagement with open innovation will increase the likelihood of introducing new processes and that the motivation to achieve legitimacy will affect this relationship. However, this moderating effect will be different depending on how engagement takes place. It will be positive on co‐operation with external parties, and negative on the use of information. Therefore, when organizations co‐operate with external parties and are motivated to achieve legitimacy, the likelihood of introducing a new process will increase. However, the effect is opposite in the case of use of external information. These findings contribute to the understanding of the relationship between open and process innovation.
Impact of diet composition and temperature–humidity index on water and dry matter intake of high‐yielding dairy cows
Authors: Ammer S. , Lambertz C. , von Soosten D. , Zimmer K. , Meyer U. , Dänicke S. , Gauly M.
Published: March 2017

The temperature–humidity index (THI) is widely used to characterize heat stress in dairy cattle. Diet composition is known to induce variation in metabolic‐associated heat production. However, the relationships between THI and diet are poorly characterized with regard to performance and intake behaviour. Therefore, the objectives were to evaluate the impact of THI on water intake (WI), dry matter intake (DMI) and the frequency of drinking and feeding bouts in lactating dairy cows offered four dietary treatments: each contained 20% grass silage and additionally (i) 20% maize silage, 60% concentrate (M‐HC); (ii) 60% maize silage, 20% concentrate (M‐LC); (iii) 20% pressed beet pulp silage, 60% concentrate (BPS‐HC); or (iv) 60% pressed beet pulp silage, 20% concentrate (BPS‐LC) (DM basis). Individual WI and DMI were recorded from April to July 2013. Furthermore, dietary effects on milk production and reticular pH were estimated. Milk yield was lowest for M‐LC, while energy‐corrected milk was similar for all diets. Milk fat percentage was higher and milk protein amount lower for cows offered both LC diets. Reticular pH below 6.3, 6.0 and 5.8 lasted longest for BPS‐LC. WI was higher for HC diets. However, the frequency of drinking bouts was not influenced by the ration. Lower DMI occurred for BPS‐LC compared to M‐LC. Frequency of feeding bouts was significantly higher for LC diets. THI was significantly related to WI, DMI as well as drinking and feeding bouts. Per increasing THI, WI increased slightly more for LC diets and DMI decreased more for HC diets. Frequency of drinking bouts increased slightly higher for BPS rations per rising THI, while the decrease in feeding bouts was highest for M‐HC. In conclusion, TMR composition and moderate heat stress impacted WI and DMI of dairy cows, while both dietary energy density and ruminal filling might intensify the THI impact.
Effect of dietary polyphenol‐rich grape seed on growth performance, antioxidant capacity and ileal microflora in broiler chicks
Authors: Abu Hafsa S. H. , Ibrahim S. A.
Published: March 2017

In this study, we examined the effect of dietary supplementation with grape seed (GS) on the performance, carcass traits, plasma biochemistry, antioxidant status and ileal microflora in broilers. Experiment diets included a control diet (without additive) and three levels of GS powder (10, 20 and 40 g/kg of diet). Each diet was fed to a total of 300 one‐day‐old Cobb‐500 chicks for 42 days. The addition of 20 g/kg of GS to the basal diet increased final body weight and body weight gain, improved the feed conversion ratio and did not affect feed intake. Dietary 20 g GS significantly increased (p < .05) the percentage of carcass yield %, dressing % and gizzard. However, the addition of 40 g/kg of GS significantly reduced the percentage of abdominal fat in the birds. Diets supplemented with GS showed the lowest content of ether extract compared with the control group (p < .05). The physical characteristics of meat and the chemical composition of DM, CP and ash were not significantly influenced by treatments. In the GS groups, plasma protein, albumin, globulin, aspartate aminotransferase and alanine aminotransferase concentrations showed no significant change compared with the control group. Broilers fed a diet supplemented with GS had lower levels of plasma glucose, total lipids, triglycerides and cholesterol compared with the control birds (p < .05). The addition of 40 g of GS significantly (p < .05) enhanced the activity of reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and GST, and correlated with significantly decreased thiobarbituric acid‐reactive substances levels compared with the control group. The value of ileal pH was not significantly affected by the GS levels. Broilers fed diets supplemented with GS had lower ileal Streptococcus spp. and Escherichia coli populations but higher Lactobacillus spp. populations (p < .05). No adverse effects on birds’ health were detected due to the use of GS. Thus, GS could be recommended as an herbal supplement in the diet of broiler chickens to improve performance, reduce blood lipids, enhance antioxidant capacity and decrease detrimental bacteria in the ileum.