bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of quality management systems on the performance of manufacturing firms
Authors: Kafetzopoulos Dimitrios P. , Psomas Evangelos L. , Gotzamani Katerina D.
Published: March 2015

Purpose

– The purpose of this paper is to provide additional evidence of the impact of ISO 9001 effectiveness on three dimensions of a firm’s performance, namely product quality, operational performance and business performance.

Design/methodology/approach

– The analysis includes an initial exploratory factor analysis (EFA), followed by confirmatory factor analysis (CFA) and structural equation modeling (SEM), in order to investigate the relations between the constructs of the proposed model. A sample of 287 ISO 9001 certified Greek manufacturing firms is used for this purpose.

Findings

– According to the study findings, ISO 9001 effectiveness directly contributes to product quality and operational performance. Although it has no direct impact on manufacturing firms’ business performance, it has an indirect impact through the moderator of operational performance.

Research limitations/implications

– The sample of the responding manufacturing companies is limited to small- and medium-sized enterprises (SMEs) from one country (Greece). In addition, the effects of the internal business environment and endogenous business factors have not been assessed through the present study.

Practical implications

– The study offers clear implications for managers who focus on elements that will increase the ISO 9001 effectiveness and desire to choose strategies, allocate resources and improve their firm’s performance.

Originality/value

– The present study contributes to the literature gap aiming at examining the degree to which ISO 9001 effectiveness influences the performance of certified firms. The concept of “ISO 9001 effectiveness” is introduced as the extent to which its prescribed quality objectives are met.
Applying the four-eyes principle to management decisions in the manufacturing sector
Authors: Hiebl Martin R.W.
Published: March 2015

Purpose

– This paper aims to explore the application of the four-eyes principle (4EP) to management decisions in large family firms in the manufacturing sector, a heretofore neglected area of business and management research.

Design/methodology/approach

– A theoretical analysis was first conducted of the 4EP in general and its application in family firms based on agency and stewardship theories. A qualitative field study of 15 large Austrian firms from the manufacturing sector with various degrees of family involvement was then conducted to explore how the 4EP is applied in these firms.

Findings

– From the theoretical analysis, it can be concluded that the 4EP may generally serve as a mechanism to limit agency conflicts. Due to a theoretically lower level of agency conflicts in family firms than in non-family firms, a lower application of the 4EP in family firms can be expected. However, the field study shows that large family firms also regularly adopt the 4EP and that family-managed firms demonstrate a more flexible and opportunistic usage of the 4EP, limiting both its associated downsides and advantages. The present paper further shows that such flexible 4EP usage in family-managed firms may increase their abilities to make quick business decisions and to display high levels of flexibility; however, it may also increase the risk of making suboptimal decisions and experiencing unfavorable managerial behavior as firms grow in size and international activity.

Originality/value

– This is the first paper to analyze the application of the 4EP in large family firms. Six propositions and a preliminary model of the 4EP in family firms are developed in the paper, which may lead to further research on the practical applications of the 4EP.
Prospective study of topical 5‐aminolevulinic acid photodynamic therapy for the treatment of severe adolescent acne in Chinese patients
Authors: Ma Ying , Liu Ye , Wang Qianqian , Ren Jie , Xiang Leihong
Published: March 2015

Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty‐one Chinese adolescent patients aged 12–18 years with Pillsbury III–IV severe facial acne were treated with three courses of ALA‐PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light‐emitting diode light at 633 nm with a light intensity of 75–80 mW/cm2 and a light dose of 90–96 J/cm2. Clinical assessment was conducted before and after each treatment, and at each follow‐up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4‐ and 8‐week follow ups, respectively. ALA‐PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side‐effects.
Green roof plant species diversity improves ecosystem multifunctionality
Authors: Lundholm Jeremy T.
Published: March 2015

Constructed ecosystems such as green roofs often contain monocultures or low‐diversity plant communities, but adding more plant species to these systems can increase ecosystem service provisioning. Mixture advantage, when species‐rich treatments outperform the best monocultures, is desirable in constructed ecosystems due to the cost of increasing diversity. However, there have not been any studies in constructed ecosystems that have quantitatively compared mixtures with the best monocultures for multifunctionality, and there have been few studies that have examined how provision of ecosystem services changes over time as plant communities develop. In a green roof system, I predicted (i) that the mixture advantage would be stronger for ecosystem multifunctionality than for single ecosystem functions and (ii) that ecosystem service provisioning and complementarity in above‐ground biomass would increase over time.

Fifteen monocultures of plant species from five life‐form groups (succulents, tall forbs, dwarf shrubs, creeping forbs, grasses) were compared with three‐species mixtures of the same life‐form and mixtures of species from three and five different life‐forms in a modular green roof system. Indicators of ecosystem services including above‐ground production, thermal regulation, stormwater retention, nutrient uptake and carbon sequestration and two indices of ecosystem multifunctionality were compared.

Canopy density increased over time while substrate temperature decreased, suggesting higher provisioning of valuable ecosystem services. For single services, the positive relationship between planted species richness and ecosystem service grew stronger over time, but was consistently strong over time for multifunctionality. Quantile regression indicated a weak mixture advantage for several services including both multifunctionality indices. While the effects were small, different species optimized different functions, thus multifunctioning is enhanced in more diverse mixtures by combining species that maximize different functions. Tripartite partitioning of canopy density showed that overyielding and trait‐independent complementarity fluctuated between years in response to shifts in species abundances, but dominance and trait‐dependent complementarity increased over time.

Synthesis and applications. This study provides the first evidence in a constructed ecosystem that mixtures can outperform the best monocultures for multiple ecosystem services. Mixtures of plant life‐forms can improve green roof performance. The biodiversity–ecosystem function relationships observed in natural ecosystems can also occur in novel and highly simplified engineered ecosystems.
Frost hollows of the boreal forest: a spatiotemporal perspective
Authors: Plasse Catherine , Payette Serge
Published: March 2015

Frost hollows (FH) are small, confined lichen‐dominated ecosystems surrounded by lichen woodlands. FH are impacted by repetitive frosts occurring during the growing season. We evaluated the dynamics of FH across the boreal forest in eastern Canada and assessed the influence of latitude as the main geoclimatic factor controlling their development.

The distribution and abundance of FH along 39 longitudinal transects were based on aerial photographs and field validation. Black spruce (Picea mariana) in FH and adjacent woodlands were sampled for age determination, year of tree establishment, height growth rate of spruce, and intensity and frequency of frost rings.

Most FH are located in the southern part of the boreal forest, in depressions bordered by dry, open, lichen woodlands. The inception and development of FH are not dependent on latitude but rather on the presence of lichen woodlands. Frost‐induced thúfurs and frost rings were more frequent and abundant in the southernmost FH, whereas the northernmost FH were devoid of thúfurs. Black spruce established synchronously in FH across the boreal forest, an indication of a climatic control associated with cloudier, humid conditions reducing radiative frost activity. Most FH spruce established after 1933 and peaked in the 1980s. Fewer frost events were recorded in the 1980s than in the 1990s. In the latter decade, frost events became more frequent, intense and synchronous across the boreal forest.

Synthesis. The distribution of frost hollows (FH) is related to the presence of dry lichen woodlands that exacerbate frost activity during the growing season. Synchronous frost‐ring frequency across the biome also suggests that shared climatic conditions, in particular freezing temperature, humidity and cloudiness, are at the origin of the dynamics of FH. A longer growing season creates propitious conditions for a higher frequency of frost events and more intense soil cryoturbation. FH are climate‐sensitive ecosystems which can be used as proxies of the impact of global change on the boreal biome.
Delayed Expected Loss Recognition and the Risk Profile of Banks
Authors: BUSHMAN ROBERT M. , WILLIAMS CHRISTOPHER D.
Published: March 2015

This paper investigates the extent to which delayed expected loan loss recognition (DELR) is associated with greater vulnerability of banks to three distinct dimensions of risk: (1) stock market liquidity risk, (2) downside tail risk of individual banks, and (3) codependence of downside tail risk among banks. We hypothesize that DELR increases vulnerability to downside risk by creating expected loss overhangs that threaten future capital adequacy and by degrading bank transparency, which increases financing frictions and opportunities for risk‐shifting. We find that DELR is associated with higher correlations between bank‐level illiquidity and both aggregate banking sector illiquidity and market returns (i.e., higher liquidity risks) during recessions, suggesting that high DELR banks as a group may simultaneously face elevated financing frictions and enhanced opportunities for risk‐shifting behavior in crisis periods. With respect to downside risk, we find that during recessions DELR is associated with significantly higher risk of individual banks suffering severe drops in their equity values, where this association is magnified for banks with low capital levels. Consistent with increased systemic risk, we find that DELR is associated with significantly higher codependence between downside risk of individual banks and downside risk of the banking sector. We theorize that downside risk vulnerability at the individual bank level can translate into systemic risk by virtue of DELR creating a common source of risk vulnerability across high DELR banks simultaneously, which leads to risk codependence among banks and systemic effects from banks acting as part of a herd.
Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31 Forensic Autopsy Cases
Authors: Li Yang , Li Ling , Mu Hong‐Shu , Fan Shuan‐Liang , He Fang‐Gang , Wang Zhen‐Yuan
Published: March 2015

Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospective study of 31 sudden unexpected deaths caused by AAD was conducted at Xi'an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female = 6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.
Cost and affordability of a nutritionally balanced gluten‐free diet: Is following a gluten‐free diet affordable?
Authors: Lambert Kelly , Ficken Caitlin
Published: March 2015

Aim

To determine the cost and affordability of a gluten‐free healthy food basket for four reference families in Australia. A secondary aim was to determine the price differential between commonly available gluten‐free and gluten‐containing food staples.

Methods

Exploratory study using an amalgamation of two commonly used food basket costing methods. Two food basket types were constructed for four common Australian family types. These were designated the Healthy Food Basket and modified (gluten‐free) Healthy Food Basket. Baskets were priced at five locations and costs as a proportion of the Equivalised Household Disposable Income and average weekly earnings for welfare recipients were calculated. The price differential for four common bread and cereal staples were also calculated per 100 g.

Results

The gluten‐free healthy food basket was significantly more expensive compared to a gluten‐containing healthy food basket for all family types. The gluten‐free basket was considered unaffordable for three of the four common family types. Gluten‐free staples are significantly more expensive than their gluten‐containing counterparts.

Conclusions

Compliance to a gluten‐free diet may be more difficult for some families due to the significant price discrepancy of gluten‐free items. Families on welfare with people who require a gluten‐free diet are particularly vulnerable to food insecurity. Consideration should be given to the creation of a national subsidised medical foods program to enable equitable access to affordable gluten‐free staple foods via prescription.
Soy milk consumption, markers of inflammation and oxidative stress in women with rheumatoid arthritis: A randomised cross‐over clinical trial
Authors: Mohammad‐Shahi Majid , Mowla Karim , Haidari Fatemeh , Zarei Mehdi , Choghakhori Razieh
Published: March 2015

Aim

The purpose of the present study was to determine the effects of soy milk consumption compared with cow's milk on inflammatory and oxidative stress markers among women with rheumatoid arthritis.

Methods

This randomised, cross‐over clinical trial was conducted on 25 patients (mean age: 45.72 years) with rheumatoid arthritis. Subjects were randomly assigned to two groups and were asked to follow a diet containing cow's milk or soy milk for four weeks. After the interventional period, a washout period was conducted for two weeks. Then groups followed the alternate treatment for four weeks.

Results

Soy milk consumption compared with cow's milk resulted in a significant difference in percent changes regarding serum levels of hs‐CRP (−13.81 ± 5.39 vs 9.21 ± 6.33%; P = 0.008) and tumour necrosis factor‐α (TNF‐α) (−15.35 ± 4.30 vs 8.11 ± 8.80%; P = 0.020). The results were not changed even after adjustment for weight. Soy milk consumption also reduced adiponectin levels significantly (baseline: 38.39 ± 2.04, end: 30.71 ± 1.93; P < 0.001). However, this reduction was not significant compared with cow's milk (P = 0.065). Soy milk consumption had no significant effects on other inflammatory factors and malondialdehyde levels.

Conclusions

Soy milk consumption for four weeks resulted in a significant improvement in some inflammatory markers (TNF‐α and hs‐CRP). However, further investigations are needed to confirm these effects.
Knowledge, use and perceptions of probiotics and prebiotics in hospitalised patients
Authors: Betz Melanie , Uzueta Anne , Rasmussen Heather , Gregoire Mary , Vanderwall Cassandra , Witowich Gretchen
Published: March 2015

Aim

Little is known about inpatient probiotic and prebiotic consumption or beliefs, despite their increase in availability. Therefore, the purpose of this research was to assess inpatient knowledge, use and perceptions of probiotics and prebiotics.

Methods

All subjects were inpatients at two urban medical centres on general medical/surgical floors. Patients were randomly selected to complete a verbally administered questionnaire inquiring about probiotic and prebiotic knowledge, use and perceptions. Patient responses were recorded directly into Survey Monkey (Palo Alto, CA, USA) on a computer.

Results

Patients (n = 200) were 58% were women and 56% were Caucasian with a mean age of 56 years. More patients were familiar with the term ‘probiotic’ (43%) compared with ‘prebiotic’ (11%); however, only 20% and 7% could correctly define probiotics and prebiotics, respectively, from a list of responses. More patients were consuming probiotics (53%) than prebiotics (38%). The most common probiotic and prebiotic products consumed were yogurts (72%) and cereals/granola bars (55%), respectively. Patients believed probiotics and prebiotics most beneficial for ‘digestion or gut health’, but the most common reason to consume these products was ‘to taste or try’ (36% and 43%, respectively). Overall, patients believed probiotics and prebiotics to be safe; however, they also believed that health claims could only somewhat be trusted.

Conclusions

This research found that many patients are consuming probiotic and prebiotic products despite limited awareness of the true meaning of these terms. As probiotic and prebiotic use is more common, it is important that clinicians are aware of increased use and provide patients with recommendations based on recent research.
Clinically Significant Differences in Acute Pain Measured on Self‐report Pain Scales in Children
Authors: Tsze Daniel S. , Hirschfeld Gerrit , von Baeyer Carl L. , Bulloch Blake , Dayan Peter S.
Published: March 2015

Objectives

The objective was to determine the minimum and ideal clinically significant differences (MCSD, ICSD) in pain intensity in children for the Faces Pain Scale–Revised (FPS‐R) and the Color Analog Scale (CAS) and to identify any differences in these estimates based on patient characteristics.

Methods

This was a prospective study of children aged 4 to 17 years with acute pain presenting to two urban pediatric emergency departments. Participants self‐reported their pain intensity using the FPS−R and CAS and qualitatively described their changes in pain. Changes in pain score reported using the FPS‐R and CAS that were associated with “a little less” and “much less” pain (MCSD and ICSD, respectively) were identified using a receiver operating characteristic–based method and expressed as raw change score and percent reductions. Estimates of MCSD and ICSD were determined for each category of initial pain intensity (mild, moderate, and severe) and patient characteristics (age, sex, and ethnicity). Post hoc exploratory analyses evaluated categories of race, primary language, and etiology of pain.

Results

A total of 314 children with acute pain were enrolled; mean (±SD) age was 9.8 (±3.8) years. The FPS‐R raw change score and percent reduction MCSD estimates were 2/10 and 25%, with ICSD estimates of 3/10 and 60%. For the CAS, raw change score and percent reduction MCSD estimates were 1/10 and 15%, with ICSD estimates of 2.75/10 and 52%. For both scales, raw change score and percent reduction estimates of the MCSD remained unchanged in children with either moderate or severe pain. For both scales, estimates of ICSD were not stable across categories of initial pain intensity. There was no difference in MCSD or ICSD based on age, sex, ethnicity, race, primary language, or etiology of pain.

Conclusions

The MCSD estimates can be expressed as raw change score and percent reductions for the FPS‐R and CAS. These estimates appear stable for children with moderate to severe pain, irrespective of age, sex, and ethnicity. Estimates of ICSD were not stable across different categories of initial pain intensity, therefore limiting their potential generalizability.
The Primacy of Race in the Geography of Income‐Based Voting: New Evidence from Public Voting Records
Authors: Hersh Eitan D. , Nall Clayton
Published: March 2015

Why does the relationship between income and partisanship vary across U.S. regions? Some answers to this question have focused on economic context (in poorer environments, economics is more salient), whereas others have focused on racial context (in racially diverse areas, richer voters oppose the party favoring redistribution). Using 73 million geocoded registration records and 185,000 geocoded precinct returns, we examine income‐based voting across local areas. We show that the political geography of income‐based voting is inextricably tied to racial context, and only marginally explained by economic context. Within homogeneously nonblack localities, contextual income has minimal bearing on the income‐party relationship. The correlation between income and partisanship is strong in heavily black areas of the Old South and other areas with a history of racialized poverty, but weaker elsewhere, including in urbanized areas of the South. The results demonstrate that the geography of income‐based voting is inseparable from racial context.
Parental allergic disease before and after child birth poses similar risk for childhood allergies
Authors: Fuertes E. , Standl M. , von Berg A. , Lehmann I. , Hoffmann B. , Bauer C.‐P. , Koletzko S. , Berdel D. , Heinrich J.
Published: March 2015

Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis, and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre‐vspost‐child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma.
A Simulator for Twenty20 Cricket
Authors: Davis Jack , Perera Harsha , Swartz Tim B.
Published: March 2015

This paper develops a Twenty20 cricket simulator for matches between sides belonging to the International Cricket Council. As input, the simulator requires the probabilities of batting outcomes which are dependent on the batsman, the bowler, the number of overs consumed and the number of wickets lost. The determination of batting probabilities is based on an amalgam of standard classical estimation techniques and a hierarchical empirical Bayes approach where the probabilities of batting outcomes borrow information from related scenarios. Initially, the probabilities of batting outcomes are obtained for the first innings. In the second innings, the target score obtained from the first innings affects the aggressiveness of batting during the second innings. We use the target score to modify batting probabilities in the second innings simulation. This gives rise to the suggestion that teams may not be adjusting their second innings batting aggressiveness in an optimal way. The adequacy of the simulator is addressed through various goodness‐of‐fit diagnostics.
The effects of counseling on fear of childbirth
Authors: Larsson Birgitta , Karlström Annika , Rubertsson Christine , Hildingsson Ingegerd
Published: March 2015

Objective

To investigate women's experiences of attending existing counseling programs for childbirth‐related fear and the effect of this counseling over time.

Design

A longitudinal survey.

Setting

Three hospitals in the central north of Sweden.

Sample

A selected sample of 936 women. Of these, 70 received counseling due to fear of childbirth (study‐group).

Methods

Data were collected with questionnaires 2 months and 1 year after giving birth with background data collected during midpregnancy. Comparisons were made between women with or without counseling. Crude and adjusted odds ratios (OR) were calculated.

Main outcome measures

Self‐reported childbirth fear, experience of counseling, birth experience and preferred mode of birth.

Results

Women in the counseling group reported higher childbirth fear 1 year after giving birth (OR 5.0, 95% confidence interval (95% CI) 2.6–9.3), they had a more negative birth experience that did not change over time (OR 2.1, 95% CI 1.2–3.9) and they preferred cesarean section to a greater extent (OR 12.0, 95% CI 5.1–28.1) in the case of another birth. Also, they were more often delivered by planned cesarean section (OR 4.7, 95% CI 2.4–9.1). However, 80% were satisfied with the given support.

Conclusion

Although women were satisfied with the treatment, this study shows that counseling had a minor effect on fear of childbirth, birth experiences or cesarean section rates. To help women with their fear of childbirth, more effective methods of treatment are needed.
Psychological functioning of people living with chronic pain: A meta‐analytic review
Authors: Burke Anne L. J. , Mathias Jane L. , Denson Linley A.
Published: March 2015

Objectives

Chronic pain (CP; >3 months) is a common condition that is associated with significant psychological problems. Many people with CP do not fit into discrete diagnostic categories, limiting the applicability of research that is specific to a particular pain diagnosis. This meta‐analysis synthesized the large extant literature from a general CP, rather than diagnosis‐specific, perspective to systematically identify and compare the psychological problems most commonly associated with CP.

Methods

Four databases were searched from inception to December 2013 (PsychINFO, The Cochrane Library, Scopus, and PubMed) for studies comparing the psychological functioning of adults with CP to healthy controls. Data from 110 studies were meta‐analysed and Cohen's d effect sizes calculated.

Results

The CP group reported experiencing significant problems in a range of psychological domains (depression, anxiety, somatization, anger/hostility, self‐efficacy, self‐esteem and general emotional functioning), with the largest effects observed for pain anxiety/concern and somatization; followed by anxiety and self‐efficacy; and then depression, anger/hostility, self‐esteem and general emotional functioning.

Conclusions

This study demonstrates, for the first time, that individuals with CP are more likely to experience physically focussed psychological problems than other psychological problems and that, unlike self‐efficacy, fear of pain is intrinsically tied to the CP experience. This challenges the prevailing view that, for individuals with CP, problems with depression are either equal to, or greater than, problems with anxiety, thereby providing important information to guide therapeutic targets.

Practitioner points

Positive clinical implications

This is the first time that the CP literature has been synthesized from a general perspective to examine psychological functioning in the presence of CP and provide practical recommendations for assessment and therapy.

Individuals with CP were most likely to experience psychological problems in physically focussed areas – namely pain anxiety/concern and somatization.

Although fear of pain was intrinsically tied to the CP experience, self‐efficacy was not.

CP was more strongly associated with anxiety than with depression.

Limitations

The study focuses on the general CP literature, adults and research‐utilizing self‐report measures.

Meta‐analyses are limited by the empirical literature on which they are based.
The predictive accuracy of intertemporal‐choice models
Authors: Arfer Kodi B. , Luhmann Christian C.
Published: March 2015

How do people choose between a smaller reward available sooner and a larger reward available later? Past research has evaluated models of intertemporal choice by measuring goodness of fit or identifying which decision‐making anomalies they can accommodate. An alternative criterion for model quality, which is partly antithetical to these standard criteria, is predictive accuracy. We used cross‐validation to examine how well 10 models of intertemporal choice could predict behaviour in a 100‐trial binary‐decision task. Many models achieved the apparent ceiling of 85% accuracy, even with smaller training sets. When noise was added to the training set, however, a simple logistic‐regression model we call the difference model performed particularly well. In many situations, between‐model differences in predictive accuracy may be small, contrary to long‐standing controversy over the modelling question in research on intertemporal choice, but the simplicity and robustness of the difference model recommend it to future use.
Atenolol offers better protection than clonidine against cardiac injury in kainic acid‐induced status epilepticus
Authors: Read M I , Harrison J C , Kerr D S , Sammut I A
Published: March 2015

Background and Purpose

Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology.

Experimental Approach

Sprague‐Dawley rats (male, 300–350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA‐induced seizures. Animals were randomized into saline controls, and saline vehicle‐, clonidine‐ or atenolol‐pretreated KA groups.

Key Results

KA administration in the saline‐pretreated group produced an immediate bradycardic response (maximal decrease of 28 ± 6%), coinciding with low‐level seizure activity. As high‐level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 ± 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA‐induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline‐pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline‐KA group.

Conclusions and Implications

Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus.
A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway
Authors: Yin Qian , Lu Haiyan , Bai Yajun , Tian Aiju , Yang Qiuxiang , Wu Jimin , Yang Chengzhi , Fan Tai‐Ping , Zhang Youyi , Zheng Xiaohui , Zheng Xiaopu , Li Zijian
Published: March 2015

Background and Purpose

Cardiac fibrosis is a common feature of advanced coronary heart disease and is characteristic of heart disease. However, currently available drugs against cardiac fibrosis are still very limited. Here, we have assessed the role of isopropyl 3‐(3,4‐dihydroxyphenyl)‐2‐hydroxylpropanoate (IDHP), a new metabolite of Danshen Dripping Pills, in cardiac fibrosis mediated by the β‐adrenoceptor agonist, isoprenaline, and its underlying mechanisms.

Experimental Approach

Identification of IDHP was identified by mass spectrometry, and proton and carbon nuclear magnetic resonance spectra. Myocardial collagen was quantitatively assessed with Picrosirius Red staining. Expression of mRNA for collagen was evaluated with real‐time PCR. Phosphorylated and total p38 MAPK, NADPH oxidase (NOX) and superoxide dismutase (SOD) were analysed by Western blot. Generation of reactive oxygen species (ROS) generation was evaluated by dihydroethidium (DHE) fluorescent staining. NOX2 was knocked down using specific siRNA.

Key Results

IDHP attenuated β‐adrenoceptor mediated cardiac fibrosis in vivo and inhibited isoprenaline‐induced proliferation of neonatal rat cardiac fibroblasts (NRCFs) and collagen I synthesis in vitro. Phosphorylation of p38 MAPK, which is an important mediator in the pathogenesis of isoprenaline‐induced cardiac fibrosis, was inhibited by IDHP. This inhibition of phospho‐p38 by IDHP was dependent on decreased generation of ROS. These effects of IDHP were abolished in NRCFs treated with siRNA for NOX2.

Conclusions and Implications

IDHP attenuated the cardiac fibrosis induced by isoprenaline through a NOX2/ROS/p38 pathway. These novel findings suggest that IDHP is a potential pharmacological candidate for the treatment of cardiac fibrosis, induced by β‐adrenoceptor agonists.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
cAMP‐dependent activation of protein kinase A as a therapeutic target of skin hyperpigmentation by diphenylmethylene hydrazinecarbothioamide
Authors: Shin Hyoeun , Hong Seung Deok , Roh Eunmiri , Jung Sang‐Hun , Cho Won‐Jea , Hong Park Sun , Yoon Da Young , Ko Seon Mi , Hwang Bang Yeon , Hong Jin Tae , Heo Tae‐Young , Han Sang‐Bae , Kim Youngsoo
Published: March 2015

Background and Purpose

cAMP as a second messenger stimulates expression of microphthalmia‐associated transcription factor (MITF) or the tyrosinase gene in UVB‐induced skin pigmentation. Diphenylmethylene hydrazinecarbothioamide (QNT 3‐80) inhibits α‐melanocyte‐stimulating hormone (α‐MSH)‐induced melanin production in B16 murine melanoma cells but its molecular basis remains to be defined. Here, we investigated the mechanism underlying the amelioration of skin hyperpigmentation by QNT 3‐80.

Experimental Approach

We used melanocyte cultures with raised levels of cAMP and UVB‐irradiated dorsal skin of guinea pigs for pigmentation assays. Immunoprecipitation, kemptide phosphorylation, fluorescence analysis and docking simulation were applied to elucidate a molecular mechanism of QNT 3‐80.

Key Results

QNT 3‐80 inhibited melanin production in melanocyte cultures with elevated levels of cAMP, including those from human foreskin. This compound also ameliorated hyperpigmentation in vivo in UVB‐irradiated dorsal skin of guinea pigs. As a mechanism, QNT 3‐80 directly antagonized cAMP binding to the regulatory subunit of PKA, nullified the dissociation and activation of inactive PKA holoenzyme in melanocytes and fitted into the cAMP‐binding site on the crystal structure of human PKA under the most energetically favourable simulation. QNT 3‐80 consequently inhibited cAMP‐ or UVB‐induced phosphorylation (activation) of cAMP‐responsive element‐binding protein in vitro and in vivo, thus down‐regulating expression of genes for MITF or tyrosinase in the melanogenic process.

Conclusions and Implications

Our data suggested that QNT 3‐80 could contribute significantly to the treatment of skin disorders with hyperpigmented patches with the cAMP‐binding site of PKA as its molecular target.
Future technology insight: mass spectrometry imaging as a tool in drug research and development
Authors: Cobice D F , Goodwin R J A , Andren P E , Nilsson A , Mackay C L , Andrew R
Published: March 2015

In pharmaceutical research, understanding the biodistribution, accumulation and metabolism of drugs in tissue plays a key role during drug discovery and development. In particular, information regarding pharmacokinetics, pharmacodynamics and transport properties of compounds in tissues is crucial during early screening. Historically, the abundance and distribution of drugs have been assessed by well‐established techniques such as quantitative whole‐body autoradiography (WBA) or tissue homogenization with LC/MS analysis. However, WBA does not distinguish active drug from its metabolites and LC/MS, while highly sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI) can discriminate drug and its metabolites and endogenous compounds, while simultaneously reporting their distribution. MSI data are influencing drug development and currently used in investigational studies in areas such as compound toxicity. In in vivo studies MSI results may soon be used to support new drug regulatory applications, although clinical trial MSI data will take longer to be validated for incorporation into submissions. We review the current and future applications of MSI, focussing on applications for drug discovery and development, with examples to highlight the impact of this promising technique in early drug screening. Recent sample preparation and analysis methods that enable effective MSI, including quantitative analysis of drugs from tissue sections will be summarized and key aspects of methodological protocols to increase the effectiveness of MSI analysis for previously undetectable targets addressed. These examples highlight how MSI has become a powerful tool in drug research and development and offers great potential in streamlining the drug discovery process.
Hunt for the origin of allergy – comparing the Finnish and Russian Karelia
Authors: Haahtela T. , Laatikainen T. , Alenius H. , Auvinen P. , Fyhrquist N. , Hanski I. , von Hertzen L. , Jousilahti P. , Kosunen T. U. , Markelova O. , Mäkelä M. J. , Pantelejev V. , Uhanov M. , Zilber E. , Vartiainen E.
Published: March 2015

The Finnish and Russian Karelia are adjacent areas in northern Europe, socio‐economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non‐existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti‐inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10‐year National Allergy Programme was started in 2008 to combat the epidemic in Finland.
Impact of asthma medication and familial factors on the association between childhood asthma and attention‐deficit/hyperactivity disorder: a combined twin‐ and register‐based study
Authors: Holmberg K. , Lundholm C. , Anckarsäter H. , Larsson H. , Almqvist C.
Published: March 2015

Background

Asthma and attention‐deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear.

Objective

Our aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma–ADHD relationship.

Methods

Data on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross‐twin–cross‐trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association.

Results

Asthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16–2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86–4.35) for ≥ 4 asthma attacks in the last 12 months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak.

Conclusions and Clinical Relevance

Childhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co‐existing disorders.
Use of sibling relationship reconstruction to complement traditional monitoring in fisheries management and conservation of brown trout
Authors: Ozerov Mikhail , Jürgenstein Tauno , Aykanat Tutku , Vasemägi Anti
Published: March 2015

Declining trends in the abundance of many fish urgently call for more efficient and informative monitoring methods that would provide necessary demographic data for the evaluation of existing conservation, restoration, and management actions. We investigated how genetic sibship reconstruction from young‐of‐the‐year brown trout (Salmo trutta L.) juveniles provides valuable, complementary demographic information that allowed us to disentangle the effects of habitat quality and number of breeders on juvenile density. We studied restored (n = 15) and control (n = 15) spawning and nursery habitats in 16 brown trout rivers and streams over 2 consecutive years to evaluate the effectiveness of habitat restoration activities. Similar juvenile densities both in restored and control spawning and nursery grounds were observed. Similarly, no differences in the effective number of breeders, Nb(SA), were detected between habitats, indicating that brown trout readily used recently restored spawning grounds. Only a weak relationship between the Nb(SA) and juvenile density was observed, suggesting that multiple factors affect juvenile abundance. In some areas, very low estimates of Nb(SA) were found at sites with high juvenile density, indicating that a small number of breeders can produce a high number of progeny in favorable conditions. In other sites, high Nb(SA) estimates were associated with low juvenile density, suggesting low habitat quality or lack of suitable spawning substrate in relation to available breeders. Based on these results, we recommend the incorporation of genetic sibship reconstruction to ongoing and future fish evaluation and monitoring programs to gain novel insights into local demographic and evolutionary processes relevant for fisheries management, habitat restoration, and conservation.
Dravet syndrome in Sweden: a population‐based study
Authors: Rosander Cecilia , Hallböök Tove
Published: March 2015

Aim

To assess the prevalence and incidence of Dravet syndrome in children diagnosed in Sweden between 2007 and 2011, and to describe neurological comorbidity, disease course, phenotypes, and treatment effects.

Method

All neuropaediatricians at university and county hospitals were asked to supply information for patients that matched the electro‐clinical profile of Dravet syndrome. Genetic laboratories and referral clinicians were also contacted and requested to supply information.

Results

The estimated incidence was one in 33 000 live births (95% CI 1:20 400–1:56 200) and prevalence on December 31, 2011 was one in 45 700 children aged less than 18 years of age (95% CI 1:33 800–1:63 400). The median age of the 42 children (18 males, 24 females) was 7 years (range 1–17y), the median age at seizure onset was 6 months (range 0–12mo), and the median age at diagnosis was 3 years (range 1–14y). A mutation in the SCN1A gene was found in 37 patients (88%), four were familial. Intellectual disability was diagnosed in 28 (67%) children, and 18 out of 30 patients investigated had autism spectrum disorder. Thirty participants had neurological deficits. Stiripentol, as an add‐on medication, was used in 18 patients. Among these patients, seven were seizure free, six had >50% seizure reduction, and five <50% seizure reduction.

Interpretation

This is the first population‐based study of Dravet syndrome in Sweden. Our data confirm international findings of incidence and highlights the severe and progressive course of this genetic epilepsy syndrome.
Alliance Portfolio Management: Dimensions and Performance
Authors: Castro Ignacio , Roldán José L.
Published: March 2015

Our paper contributes to the understanding of the alliance portfolio management capability by examining the relationships among their different dimensions and their impact on the alliance portfolio performance. The current study proposes and tests a multiple mediating model and tests the mediation. A variance‐based structural equation modelling (partial least squares) has been applied to a sample made up of 144 top Spanish companies. Our analysis on the one hand fosters the importance of the partnering proactiveness and their influences on the alliance portfolio performance, and, on the other, formulates mediation hypotheses, which posit how the relational governance and portfolio coordination dimensions play a critical mediating role in the partnering proactiveness – the alliance portfolio performance link. Results from the data analysis show that the dimensions of alliance portfolio management capability are related in such a way that the relational governance and the portfolio coordination: (1) partially mediate the effect of partnering proactiveness on the alliance portfolio value; and (2) exert significant influences on the alliance portfolio performance.