bluuebunny/crossref_metadata_2025 huggingface dataset:
Women in the boardroom and corporate decisions of Italian listed companies
Authors: Rossi Fabrizio , Hu Chengru , Foley Maggie
Published: July 2017

Purpose

The purpose of this paper is to investigate the relationship between women in the board of directors, firm performance and corporate decisions as well as the risk of the firm, debt level, and research and development (R&D).

Design/methodology/approach

This study investigates a sample of 41 Italian listed companies. In particular, using a panel data of 369 firm-year observations, during the period 2005-2013, through a generalized method of moment, the relationship between women in the board of directors and corporate decisions has been investigated.

Findings

The results suggest that female representation in the board of directors affects corporate decisions. Women in the boardroom affect both financing and investment decisions. In particular, the presence of women seems to take on a complementary role to debt; it has a negative effect on risk and appears to have a positive impact on investment in R&D The results also suggest a strong relationship between female directors and firm value, especially when certain multicultural factors are considered. Finally, considering the concept of “critical mass,” in line with the arguments of Kanter (1977), the results seem to emphasize a greater influence of women with respect to corporate decisions, moving from “tokenism” to a “critical mass” scenario.

Practical implications

The outcomes of the application, besides improving the current knowledge on the relationship between female representation in the board of directors, innovation, financial, and accounting decisions, intend to reveal if the governance of Italian listed companies is efficient in determining company results and in pursuing optimal decisions. Moreover, the results could be useful for both policy makers for the regulation of corporate governance and the board of directors and as a suggestion to companies that regularly appoint the members of the board of directors.

Originality/value

The work is not limited to examining the relationship between female representation and the performance of firms but instead uses a series of indicators of corporate decisions and multicultural, such as, the nationality of women in board of directors, the educational level, the past experience, and their interaction with the variables concerning the decision-making process. To the best knowledge of authors, this is the first study that investigates the relationship between women and corporate decisions in a single civil law country.
A brand-based perspective on differentiation of green brand positioning
Authors: Wang Hui-Ju
Published: July 2017

Purpose

The purpose of this paper is to offer a perspective of brand-based analysis on green brand positioning differentiation through a network analysis approach.

Design/methodology/approach

This study employs centrality and distinctiveness as bases to develop a matrix framework of green brand positioning differentiation. The two dimensions are measured from the techniques of network analysis, including analysis of the core-periphery structure and adjacency matrix.

Findings

The results yield four clusters with different positions in a 2×2 matrix, including 23 core brands with high-positioning distinctiveness, ten core brands with low-positioning distinctiveness, ten peripheral brands with high-positioning distinctiveness, and seven peripheral brands with low-positioning distinctiveness.

Research limitations/implications

The results contribute to providing brand researchers with different analytical perspectives on the existing knowledge about green brand positioning and offer strategic positioning information for green brand practitioners.

Originality/value

This research contributes to the literature in three ways. First, this research is a first attempt to offer a brand-based perspective on differentiation of green brand positioning. Second, this research advances the existing knowledge that uses network analysis on green brand positioning by offering different techniques for brand differentiation analysis. Finally, this research complements the strategic positioning information of the current business environment in the context of green branding.
Who is shaping entrepreneurial experience? A multiple case study of Chinese entrepreneurial learning
Authors: Zheng Wenzhi , Xu Miaomaio , Chen Xiaochen , Dong Yan
Published: July 2017

Purpose

The purpose of this paper is to investigate the institutions involved in providing experience to entrepreneurs in China and analyzed the types of experience they provide. Moreover, the abilities of related organizations to shape experience were analyzed.

Design/methodology/approach

By using a multiple case study method, this qualitative study examined various entrepreneurial experience providers (namely incubator, entrepreneurship training institution, franchise store, entrepreneurship training network, and family business experience transfer) to understand the experience types and their supplying competencies.

Findings

On the basis of the types of entrepreneurial experience and the criteria for entrepreneurial competency assessment, the study results showed that the primary providers in China are the Start Your Business (SYB) program, incubators, and family businesses. Furthermore, for-profit social training organizations provided less experience than did governmental or private ones. The five providers mainly provided “know-what” entrepreneurial experience. Among the providers, family businesses and SYB offered experience that was conducive to entrepreneurial learning.

Research limitations/implications

Entrepreneurs are the subjects of entrepreneurship education, while this study mainly focused on analyzing the experience supplying competencies. Thus, future studies should explore the required abilities that are developed during entrepreneurship for various learners.

Practical implications

This study interpreted how to achieve Chinese mass entrepreneurship and innovation strategy in the context of the low development of entrepreneurship higher education. To improve their competencies in providing experience, providers must focus on developing proper curricula, effective transfer methods and teacher resources, and incorporating entrepreneurship education.

Originality/value

On the basis of social learning theory and human capital theory, this study developed a set of criteria for the assessment of the ability of entrepreneurial experience providers. This study analyzed how related institutions enhanced entrepreneurial experience, thereby expanding the relevant learning channels and providing options for entrepreneurs to accumulate experience in China.
The performance of a resazurin chromogenic agar plate with a combined disc method for rapid screening of extended‐spectrum‐β‐lactamases, AmpC β‐lactamases and co‐β‐lactamases in Enterobacteriaceae
Authors: Teethaisong Yothin , Evans Katie , Nakouti Ismini , Tiamyom Kanokwan , Ketudat‐Cairns James R. , Hobbs Glyn , Eumkeb Griangsak
Published: July 2017

A promising means of rapid screening of extended‐spectrum‐β‐lactamase (ESBL), AmpC β‐lactamase, and co‐production of ESBL and AmpC that combines resazurin chromogenic agar (RCA) with a combined disc method is here reported. Cefpodoxime (CPD) discs with and without clavulanic acid (CA), cloxacillin (CX) and CA+CX were evaluated against 86 molecularly confirmed β‐lactamase‐producing Enterobacteriaceae, including 15 ESBLs, 32 AmpCs, nine co‐producers of ESBL and AmpC and 30 carbapenemase producers. The CA and CX synergy test successfully detected all ESBL producers (100% sensitivity and 98.6% specificity) and all AmpC producers (100% sensitivity and 96.36% specificity). This assay also performed well in screening for co‐existence of ESBL and AmpC (88.89% sensitivity and 100% specificity). The RCA assay is simple and inexpensive and provides results within 7 hr. It can be performed in any microbiological laboratory, in particular, in geographic regions in which ESBL, AmpC or co‐β‐lactamase‐producing Enterobacteriaceae are endemic.
Predatory birds and ants partition caterpillar prey by body size and diet breadth
Authors: Singer Michael S. , Clark Robert E. , Lichter‐Marck Issac H. , Johnson Emily R. , Mooney Kailen A.
Published: July 2017

The effects of predator assemblages on herbivores are predicted to depend critically on predator–predator interactions and the extent to which predators partition prey resources. The role of prey heterogeneity in generating such multiple predator effects has received limited attention.

Vertebrate and arthropod insectivores constitute two co‐dominant predatory taxa in many ecosystems, and the emergent properties of their joint effects on insect herbivores inform theory on multiple predator effects as well as biological control of insect herbivores.

Here we use a large‐scale factorial manipulation to assess the extent to which birds and ants engage in antagonistic predator–predator interactions and the consequences of heterogeneity in herbivore body size and diet breadth (i.e. the diversity of host plants used) for prey partitioning. We excluded birds and reduced ant density (by 60%) in the canopies of eight northeastern USA deciduous tree species during two consecutive years and measured the community composition and traits of lepidopteran larvae (caterpillars).

Birds did not affect ant density, implying limited intraguild predation between these taxa in this system. Birds preyed selectively upon large‐bodied caterpillars (reducing mean caterpillar length by 12%) and ants preyed selectively upon small‐bodied caterpillars (increasing mean caterpillar length by 6%). Birds and ants also partitioned caterpillar prey by diet breadth. Birds reduced the frequency dietary generalist caterpillars by 24%, while ants had no effect. In contrast, ants reduced the frequency of dietary specialists by 20%, while birds had no effect, but these effects were non‐additive; under bird exclusion, ants had no detectable effect, while in the presence of birds, they reduced the frequency of specialists by 40%. As a likely result of prey partitioning by body size and diet breadth, the combined effects of birds and ants on total caterpillar density were additive, with birds and ants reducing caterpillar density by 44% and 20% respectively.

These results show evidence for the role of prey heterogeneity in driving functional complementarity among predators and enhanced top‐down control. Heterogeneity in herbivore body size and diet breadth, as well as other prey traits, may represent key predictors of the strength of top‐down control from predator communities.
Invasive pathogen drives host population collapse: Effects of a travelling wave of sarcoptic mange on bare‐nosed wombats
Authors: Martin Alynn M. , Burridge Christopher P. , Ingram Janeane , Fraser Tamieka A. , Carver Scott
Published: July 2017

Emerging and invasive pathogens can have long‐lasting impacts on susceptible wildlife populations, including localized collapse and extirpation. Management of threatening disease is of widespread interest and requires knowledge of spatiotemporal patterns of pathogen spread.

Theory suggests disease spread often occurs via two patterns: homogenous mixing and travelling waves. However, high‐resolution empirical data demonstrating localized (within population) disease spread patterns are rare.

This study examined the spread of sarcoptic mange (aetiological agent Sarcoptes scabiei) in a population of bare‐nosed wombats (Vombatus ursinus), and investigated whether pathogen spread occurred by homogenous mixing or a travelling wave.

Using 7 years of population surveys and 4 years of disease severity surveys, we show that mange was first detected in the east of a wombat population in northern Tasmania, and progressed westward as a travelling wave. Wombat mortality rates reached 100% behind the wave, with a 94% decline in overall wombat abundance within the park.

Synthesis and applications. Globally distributed pathogens may have severe impacts on susceptible host species. This is the first study to quantify population‐level impacts of sarcoptic mange upon bare‐nosed wombats, showing a wave of mange disease which resulted in a dramatic population decline. Successful management of the spread of this and similar pathogens may hinge on the capacity to establish transmission barriers at local or between‐population scales.
Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting
Authors: Lee Dale , Barsky Diane , Hughes Rachel , Driggers Julia , Poupard Nicole , Mascarenhas Maria
Published: July 2017

Aim

Practitioners often avoid administering iron dextran in parenteral nutrition (PN) for hospitalised children because of the concern for anaphylaxis. The primary aim of the present study was to determine the risk of anaphylaxis associated with exposure to PN containing iron dextran in the inpatient setting.

Methods

Charts were reviewed for all children admitted to The Children's Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received PN containing low molecular weight (LMW) iron dextran. Subject characteristics, primary diagnoses and PN orders were evaluated. The pharmacy adverse events database was queried for adverse drug reactions.

Results

Over three years, 89 subjects received PN containing a maintenance dose of LMW iron dextran with a total of 2774 days of exposure. Subjects ranged from two months to 21 years of age and received between 1 and 196 days of PN containing iron dextran. The mean dose of iron dextran in children decreased as the weight category increased from <5 kg (0.21 ± 0.05 mg/kg/day) to ≥40 kg (1.9 ± 0.5 mg/day; P‐value for trend <0.005). No anaphylactic reactions occurred in any subjects.

Conclusions

PN containing a maintenance dose of LMW iron dextran can be safely administered to hospitalised children, and further studies are need to evaluate the potential to prevent iron deficiency anaemia and the need for additional IV iron infusions.
Efficacy of a telephone‐based medical nutrition program on blood lipid and lipoprotein metabolism: Results of Our Healthy Heart
Authors: Miller Kelsey E. , Martz Daniel C. , Stoner Cathey , Jowers Audrey , Taheri Megan L. , Sarzynski Mark A. , Davis Rachel A.H. , Plaisance Eric P.
Published: July 2017

Aim

Derangements in blood lipid and lipoprotein metabolism are one of the leading causes of coronary heart disease (CHD). Therapeutic lifestyle changes such as diet and exercise are often prescribed to improve blood lipid and lipoprotein characteristics, but the efficacy of a telephone‐based health coaching program has not been thoroughly explored. Our purpose was to examine effects of the Our Healthy Heart (OHH) Program on blood lipid and lipoprotein characteristics of individuals with mixed dyslipidaemia.

Methods

Cholesterol content of serum very low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL) and high‐density (HDL) subfractions and apolipoprotein concentrations were measured by vertical‐density ultracentrifugation (Vertical Auto Profile (VAP)) from 1522 individuals with mixed dyslipidaemia (age 18–99 years, body mass index (BMI) 25–40, 62.7% female). Telephone‐based health coaching (OHH, n = 722) or standard care (Control, n = 800) was provided for six months followed by VAP to evaluate changes in lipid and lipoprotein concentrations. Controls were obtained from individuals with similar blood lipid/lipoprotein characteristics who did not participate in the OHH Program. Coaches collected baseline self‐reported data on anthropometrics, food intake and exercise. Participants in the OHH group were then prescribed a hypocaloric 500 kcal/day caloric deficit with encouragement to participate in physical activity. A two‐way ANOVA was used to examine differences between groups over time, with results presented as means ± standard deviation.

Results

Health coaching significantly decreased serum concentrations of apoB100 (104.5 ± 25.8–94.3 ± 24.8 mg/dL), shifted LDL pattern size from B to A or A/B in over 60% of the OHH group and decreased cholesterol content of all VLDL subfractions (P < 0.05) compared to the control.

Conclusions

Telephone‐based health coaching recommendations to reduce dietary energy intake and increase physical activity produced significant improvements in cholesterol content of atherogenic lipoproteins, which are known to increase CHD risk.
Simulation‐based training program with deliberate practice for ultrasound‐guided jugular central venous catheter placement
Authors: Corvetto M. A. , Pedemonte J. C. , Varas D. , Fuentes C. , Altermatt F. R.
Published: July 2017

Background

Current evidence supports the utility of simulation training for bedside procedures such as ultrasound‐guided jugular central venous catheter (CVC) insertion. However, a standardized methodology to teach procedural skills has not been determined yet. The aim of this study was to evaluate the effectiveness of a simulation‐based training program for improving novice technical performance during ultrasound‐guided internal jugular CVC placement.

Methods

Postgraduate year 1 (PGY‐1) residents from anesthesiology, emergency medicine, cardiology, ICU, and nephrology specialties were trained in four deliberate practice sessions. Learning objectives included principles of ultrasound (US), preparation (gown, glove, draping), procedural skills I (US scanning and puncture), and procedural skills II (catheter insertion). CVC technical proficiency was tested pre‐ and post‐training using hand‐motion analysis with the Imperial College Surgical Assessment Device (ICSAD) and a global rating scale (GRS).

Results

Thirty‐five PGY‐1 residents successfully completed the program. These novices' GRS scores improved significantly after the training (P < 0.001). Total path length measured with the ICSAD decreased significantly after the training (P = 0.008). Procedural time decreased significantly after training from 387 (310–501) seconds to 200 (157–261) seconds (median and interquartile range) (P = 0.029).

Conclusion

This simulation‐training program based on deliberate practice significantly increased the technical skills of residents in US‐guided short‐axis, out‐of‐plane internal jugular CVC placement. Data also confirm the validity of the ICSAD as an assessment tool for ultrasound‐guided internal jugular CVC placement learning.
Development and evaluation of online education to increase the forensic relevance of oral health records
Authors: Stow L , Higgins D
Published: July 2017

Background

Human identification can be reliably established by dental comparison; success is significantly impacted by inadequate ante‐mortem information. Previous Australian research revealed suboptimal recording of features important for forensic dental identification and compliance with Dental Board of Australia guidelines. We hence created and evaluated an online education programme aimed at improving oral health practitioner recording.

Methods

An interactive learning module (ILM) was constructed and released to three focus groups representing practitioners with varying experience levels: Australian Society of Forensic Odontology members, third year dental students and the wider dental community. Pre‐ and post‐participation perceptions were recorded, with percentage, mean, broad agreement, standard deviation and statistical significance between responses determined.

Results

Improved recognition of importance of record keeping, knowledge, confidence, skill and motivation to learn was seen following ILM interaction. This was particularly significant for students, participants with 3–5 years of experience in their current occupation and those whose highest level of education was achieved in Australia.

Conclusions

The ILM increased self‐reported awareness, understanding and attitude of participants with different levels of case note recording experience; this can improve recording practises and aid forensic dental identification if utilized in undergraduate teaching and as a continuing professional development tool for dental practitioners.
Food intake and darunavir plasma concentrations in people living with HIV in an outpatient setting
Authors: Daskapan Alper , Dijkema Desie , de Weerd Dorien A. , Bierman Wouter F. W. , Kosterink Jos G. W. , van der Werf Tjip S. , Alffenaar Jan‐Willem C. , Stienstra Ymkje
Published: July 2017

Aims

Patients receiving darunavir are advised to take it concomitantly with food. The objectives of the present cross‐sectional study were to evaluate the actual concomitant food intake of patients visiting an HIV outpatient clinic.

Methods

Sixty participants treated with darunavir/ritonavir once daily were subjected to a food recall questionnaire concerning their last concomitant food intake with darunavir. Darunavir trough concentrations were calculated.

Results

The median food intake was 507 (0–2707) kcal; protein intake, 20 (0–221)g; carbohydrate intake, 62 (0–267)g; fat intake: 14 (0–143)g; and dietary fibre: 4 (0–30)g. Twenty‐five patients (42%) ingested their drug with between‐meal snacks. No relationship was found between food intake and trough concentrations.

Conclusions

Clear advice on the optimal caloric intake is needed, to avoid high caloric intake in patients who already have an increased risk of cardiovascular disease due to their HIV infection.
NFAT‐regulated cytokine gene expression during tacrolimus therapy early after renal transplantation
Authors: Bremer Sara , Vethe Nils T. , Skauby Morten , Kasbo Margrete , Johansson Elisabet D. , Midtvedt Karsten , Bergan Stein
Published: July 2017

Aims

Despite pharmacokinetic monitoring of calcineurin inhibitors, the long‐term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of the present study was to characterize nuclear factor of activated T cells (NFAT)‐regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy.

Methods

In 29 renal allograft recipients, samples were drawn once pre‐Tx, and before and 1.5 h after Tac dosing at approximately 1 week, 6 weeks and 1 year post‐Tx. Tac concentrations were measured by immunoassay, while the expression of genes encoding NFAT‐regulated cytokines [interleukin 2 (IL2), interferon gamma (IFNG), colony stimulating factor 2 (CSF2)] and cytochrome P450 3A5 (CYP3A5) genotyping were determined by real‐time polymerase chain reaction.

Results

The cytokine response after Tac dosing varied up to 46‐fold between patients and changed significantly with time post‐engraftment. Tac concentrations 1.5 h postdose (C1.5) >15 μg l–1 were associated with strong cytokine inhibition and residual gene expression (RGE) ≤10%, while lower Tac C1.5 resulted in more variable responses (RGE 2.5–68.7%). Patients with ongoing subclinical acute rejection (n = 5) demonstrated limited cytokine inhibition (RGE 39.7–72.6%), while patients with polyoma virus viraemia (n = 3) had relatively strong inhibition of cytokines (RGE 2.5–32.5%). By contrast, there was no association between Tac exposure and rejection or viraemia.

Conclusions

The findings of our study support the potential of NFAT‐regulated gene expression measurements as a pharmacodynamic tool for additional monitoring of Tac therapy, especially in the context of overimmunosuppression and viraemia.
Drug repurposing screens and synergistic drug‐combinations for infectious diseases
Authors: Zheng Wei , Sun Wei , Simeonov Anton
Published: July 2017

Infectious diseases account for nearly one fifth of the worldwide death toll every year. The continuous increase of drug‐resistant pathogens is a big challenge for treatment of infectious diseases. In addition, outbreaks of infections and new pathogens are potential threats to public health. Lack of effective treatments for drug‐resistant bacteria and recent outbreaks of Ebola and Zika viral infections have become a global public health concern. The number of newly approved antibiotics has decreased significantly in the last two decades compared with previous decades. In parallel with this, is an increase in the number of drug‐resistant bacteria. For these threats and challenges to be countered, new strategies and technology platforms are critically needed. Drug repurposing has emerged as an alternative approach for rapid identification of effective therapeutics to treat the infectious diseases. For treatment of severe infections, synergistic drug combinations using approved drugs identified from drug repurposing screens is a useful option which may overcome the problem of weak activity of individual drugs. Collaborative efforts including government, academic researchers and private drug industry can facilitate the translational research to produce more effective new therapeutic agents such as narrow spectrum antibiotics against drug‐resistant bacteria for these global challenges.

Linked Articles

This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction
Authors: Yamakawa Yasuaki , Tazawa Hiroshi , Hasei Joe , Osaki Shuhei , Omori Toshinori , Sugiu Kazuhisa , Komatsubara Tadashi , Uotani Kouji , Fujiwara Tomohiro , Yoshida Aki , Kunisada Toshiyuki , Urata Yasuo , Kagawa Shunsuke , Ozaki Toshifumi , Fujiwara Toshiyoshi
Published: July 2017

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor‐specific replicating oncolytic adenovirus OBP‐301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP‐301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP‐301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS‐2). The cytotoxic effect of OBP‐301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP‐301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP‐301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP‐301 and ZOL displayed a synergistic antitumor effect, in which OBP‐301 promoted apoptosis through suppression of anti‐apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor‐mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP‐301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.
Integrated analysis of SNP, CNV and gene expression data in genetic association studies
Authors: Momtaz R. , Ghanem N.M. , El‐Makky N.M. , Ismail M.A.
Published: July 2017

Integrative approaches that combine multiple forms of data can more accurately capture pathway associations and so provide a comprehensive understanding of the molecular mechanisms that cause complex diseases. Association analyses based on single nucleotide polymorphism (SNP) genotypes, copy number variant (CNV) genotypes, and gene expression profiles are the 3 most common paradigms used for gene set/pathway enrichment analyses. Many work has been done to leverage information from 2 types of data from these 3 paradigms. However, to the best of our knowledge, there is no work done before to integrate the 3 paradigms all together. In this article, we present an integrated analysis that combine SNP, CNV, and gene expression data to generate a single gene list. We present different methods to compare this gene list with the other 3 possible lists that result from the combinations of the following pairs of data: SNP genotype with gene expression, CNV genotype with gene expression, and SNP genotype with CNV genotype. The comparison is done using 3 different cancer datasets and 2 different methods of comparison. Our results show that integrating SNP, CNV, and gene expression data give better association results than integrating any pair of 3 data.
Mining for mitochondrial mechanisms: Linking known syndromes to mitochondrial function
Authors: Panneman D.M. , Smeitink J.A. , Rodenburg R.J.
Published: July 2017

Mitochondrial disorders (MDs) are caused by defects in 1 or multiple complexes of the oxidative phosphorylation (OXPHOS) machinery. MDs are associated with a broad range of clinical signs and symptoms, and have considerable clinical overlap with other neuromuscular syndromes. This overlap might be due to involvement of mitochondrial pathways in some of these non‐mitochondrial syndromes. Here, we give an overview of around 25 non‐mitochondrial syndromes, diagnosed in patients who were initially suspected to have a MD on the basis of clinical and biochemical parameters. In addition, we highlight the mitochondrial connections of 6 of these non‐mitochondrial syndromes (eg, Rett syndrome and Dravet syndrome) diagnosed in multiple patients. Further research to unravel the interplay between these genes and mitochondria may help to increase knowledge on these syndromes. Additionally, it may open new avenues for research on pathways interacting with mitochondrial function in order to find new targets for therapeutics to treat MDs. The data presented in this review underline the importance of careful assessment of clinical, genetic, and biochemical data in all patients suspected of a neuromuscular syndrome, and highlights the importance of the role of clinical geneticists, physicians, and clinical biochemists in recognizing the possible mitochondrial connection of non‐mitochondrial syndromes.
Simultaneous patch testing with fragrance mix I, fragrance mix II and their ingredients in southern Sweden between 2009 and 2015
Authors: Mowitz Martin , Svedman Cecilia , Zimerson Erik , Isaksson Marléne , Pontén Ann , Bruze Magnus
Published: July 2017

Background

Fragrance mix I (FM I) and fragrance mix II (FM II) are included in the European baseline series as screening substances for fragrance contact allergy.

Objectives

To investigate the frequency of allergic reactions to FM I, FM II and their ingredients in consecutively patch tested patients.

Materials and methods

A retrospective analysis of data from 4430 patients patch tested between 2009 and 2015 was performed.

Results

Of the patients, 6.5% were FM I‐positive and 3.2% were FM II‐positive. Forty‐five per cent of FM I‐positive patients did not have positive reactions to FM I ingredients. Thirty‐five per cent of those who were FM II‐positive did not have positive reactions to FM II ingredients. Twenty‐seven per cent of those with positive reactions to one or more of the FM I ingredients were FM I‐negative, and 36% of those who had positive reactions to one or more of the FM II ingredients were FM II‐negative. The allergens with the highest pick‐up rates were Evernia prunastri (1.8%), cinnamal (1.3%), citral (1.2%), and hydroxyisohexyl 3‐cyclohexene carboxaldehyde (1.2%). Significant differences were observed in the proportions of positive reactions to FM I, FM II, eugenol, isoeugenol, and farnesol when results from patch testing with materials from different suppliers were compared.

Conclusions

There is a risk of missing fragrance contact allergy when testing with only the fragrance mixes is performed. The use of preparations from different suppliers may affect the patch test results.
Lipoid proteinosis: A case with distinct histopathological and radiological findings
Authors: Brar Balvinder Kaur , Jain Sarina , Brar Sukhmani Kaur
Published: July 2017

Lipoid proteinosis is a rare inherited genodermatosis characterized by hyaline deposits in various tissues. Clinically, it manifests with cutaneous as well as extracutaneous features. Periodic acid‐Schiff (PAS)‐reactive hyaline deposits in the upper dermis, with localization around blood vessels and eccrine sweat glands, in particular, is the histopathological hallmark finding. On brain imaging, bilateral symmetrical temporal lobe calcifications are considered to be pathognomonic of this disorder. We report a case of lipoid proteinosis in which hyaline deposits were present in the papillary and reticular dermis, without being seen at the periphery of eccrine sweat glands, along with dystrophic calcification. Magnetic resonance imaging (MRI) of brain revealed hydrocephalus, subependymal heterotropia and absent splenium of corpus callosum with no evidence of temporal lobe calcification. Thus, our case highlights the inherent diverse nature of lipoid proteinosis.
Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?
Authors: Petrykiv Sergei , Laverman Gozewijn D. , de Zeeuw Dick , Heerspink Hiddo J. L.
Published: July 2017

Individual patients show a large variation in their response to renin‐angiotensin‐aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium‐glucose co‐transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer cardiovascular and, possibly, renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor, we assessed individual albuminuria responses in patients exposed to both RAASi and the SGLT2 inhibitor dapagliflozin. We used data from a randomized controlled cross‐over trial designed to assess the albuminuria‐lowering effect of 6‐week treatment with dapagliflozin 10 mg/d. We extracted from the electronic medical records data on the albuminuria response upon initiation of RAASi before the trial period, and analysed individual albuminuria responses to RAASi and to dapagliflozin. We retrieved data on RAASi for 26 patients (age, 62 years [SD, 8]; female gender, 6 [23%]; 24‐hour urinary albumin excretion, 521 [187‐921] mg/24 h). The mean albuminuria‐lowering response to RAASi was 26.5% (range, −76.1% to 135.1%). The addition of dapagliflozin res in a further reduction of 34.9%, (range, −83.9 to 94.2). Interestingly, the albuminuria response to RAASi significantly correlated with the response to dapagliflozin (Pearson correlation coefficient, 0.635 [95% CI, 0.328‐0.821]; P < .001), indicating that patients who did not respond to RAASi also did not respond to dapagliflozin. We concluded that individual therapy resistance to RAASi cannot be overcome with the addition of a completely different class of drugs, SGLT2 inhibitors. These data suggest that the individual drug response is an intrinsic individual characteristic, possibly unrelated to the type of intervention, unless the mode of action of dapagliflozin on albuminuria is through the RAAS.
In‐situ prediction of soil organic carbon by vis–NIR spectroscopy: an efficient use of limited field data
Authors: Kühnel A. , Bogner C.
Published: July 2017

Visible–near‐infrared diffuse reflectance spectroscopy (vis–NIR DRS) has been widely used to predict soil organic carbon (SOC) in the laboratory. Predictions made directly from soil spectra measured in situ under field conditions, however, remain challenging. This study addresses the issue of incorporating in‐situ reflectance spectra efficiently into calibration data when a few field measurements only are available. We applied the synthetic minority oversampling technique (SMOTE) to generate new data with in‐situ reflectance spectra from soil profiles. Subsequently, we combined existing spectral libraries with these new synthetic data to predict SOC by partial least squares regression (PLSR). We found that models with added synthetic spectra always outperformed models based on the spectral libraries alone and in most cases also those with added in‐situ spectra only. We used the models to predict the distribution of SOC in soil profiles under five different land uses at Mount Kilimanjaro (Tanzania). Based on our results, we propose a framework for predicting SOC with a limited number of in‐situ soil spectra. This framework could effectively reduce the costs of developing in‐situ models for SOC at the local scale.

Highlights

We compare predictions of soil organic carbon from spectra of dried and sieved samples, field samples and calculated spectra.

We use the synthetic minority oversampling technique (SMOTE) to calculate new soil spectra.

Models with SMOTE outperform models with dried and field spectra in most cases.

SMOTE can be used to reduce prediction errors when a few field data only are available for calibration.
hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma
Authors: Zhu Xiaoli , Wang Xiyong , Wei Shuzhen , Chen Yan , Chen Yang , Fan Xiaobo , Han Shuhua , Wu Guoqiu
Published: July 2017

Circular RNAs (circRNAs) are associated with cancer progression and metastasis, although little is known about their role in lung adenocarcinoma (LAC). In the present study, microarrays were first used to screen for tumour‐specific circRNA candidates in LAC tissue. Thirty‐nine circRNAs were found to be up‐regulated and 20 were down‐regulated (fold change > 2.0). Among them, hsa_circ_0013958 was further confirmed to be up‐regulated in all of the LAC tissues, cells and plasma. In addition, hsa_circ_0013958 levels were associated with TNM stage (P = 0.009) and lymphatic metastasis (P = 0.006). The area under the receiver operating characteristic curve was 0.815 (95% confidence interval = 0.727–0.903; P < 0.001). In addition, to further illustrate the bioactivities of hsa_circ_0013958 in LAC, siRNA‐mediated inhibition of hsa_circ_0013958 was performed in vitro. The results showed that hsa_circ_0013958 promoted cell proliferation and invasion and inhibited cell apoptosis in LAC. Moreover, hsa_circ_0013958 was identified as a sponge of miR‐134, and thus it up‐regulated oncogenic cyclin D1, which plays a pivotal role in the development of non‐small cell lung cancer. In conclusion, our results suggested that hsa_circ_0013958 could be used as a potential non‐invasive biomarker for the early detection and screening of LAC.
PD‐1/PD‐L1 inhibitors in haematological malignancies: update 2017
Authors: Jelinek Tomas , Mihalyova Jana , Kascak Michal , Duras Juraj , Hajek Roman
Published: July 2017

The introduction of PD‐1/PD‐L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice‐changing activity in various types of solid tumours. Among haematological malignancies, PD‐1/PD‐L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over‐expression of PD‐1 ligands (PD‐L1, PD‐L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication. Although the results in other lymphoid malignancies have not been so striking, blockade of the PD‐1/PD‐L1 axis has led to meaningful responses in other lymphoma types such as diffuse large B‐cell lymphoma, follicular lymphoma or several T‐cell lymphomas. Monotherapy with PD‐1/PD‐L1 inhibitors in chronic lymphocytic leukaemia and multiple myeloma has been unsatisfactory, suggesting that a combinational approach with other synergistic drugs is needed. In the case of multiple myeloma, immunomodulatory agents together with corticosteroids represent the most promising combinations. Among myeloid malignancies, the anti‐PD‐1 monoclonal antibodies are examined dominantly in acute myeloid leukaemia and myelodysplastic syndromes in combination with potentially synergistic hypomethylating drugs such as 5‐azacitidine, resulting in promising outcomes that warrant further investigation. We have described all available clinical results of PD‐1/PD‐L1 inhibitors in haematological malignancies and discussed related toxicities, as well as highlighted crucial preclinical studies in this review.
PI3K‐Akt pathway enhances the differentiation of interleukin‐27‐induced type 1 regulatory T cells
Authors: Nadya Niken Adiba , Tezuka Hiroyuki , Ohteki Toshiaki , Matsuda Satoshi , Azuma Miyuki , Nagai Shigenori
Published: July 2017

Interleukin 27 (IL‐27) has been identified as a potent cytokine in the differentiation of type 1 regulatory T (Tr1) cells through interactions with several key elements, including transcription factors such as aryl hydrocarbon receptor and IL‐21. Autocrine production of IL‐21 is known to be important for maintaining IL‐10 expression by Tr1 cells. Although previous studies have shown that the phosphoinositide 3‐kinase (PI3K) –Akt axis contributes to the differentiation of helper T‐cell subsets, the role of the PI3K pathway on Tr1 cell differentiation remains to be elucidated. Here, we demonstrate that suppression of the PI3K‐Akt pathway results in impairment of IL‐27‐induced Tr1 (IL‐27–Tr1) cell differentiation in vitro and in vivo. Furthermore, this suppression down‐regulates IL‐21 receptor expression by Tr1 cells, followed by suppression of IL‐10 expression by IL‐27–Tr1 cells. These results suggest that the PI3K pathway enhances IL‐10 expression by IL‐27–Tr1 cells through up‐regulation of IL‐21 receptors.
Role of inbreeding depression, non‐inbred dominance deviations and random year‐season effect in genetic trends for prolificacy in closed rabbit lines
Authors: Fernández E.N. , Sánchez J.P. , Martínez R. , Legarra A. , Baselga M.
Published: July 2017

In closed rabbit lines selected for prolificacy at the Polytechnic University of Valencia, genetic responses are predicted using BLUP. With a standard additive BLUP model and year‐season (YS) effects fitted as fixed, genetic trends were overestimated compared to responses estimated using control populations obtained from frozen embryos. In these lines, there is a confounding between genetic trend, YS effects and inbreeding, and the role of dominance is uncertain. This is a common situation in data from reproductively closed selection lines. This paper fits different genetic evaluation models to data of these lines, aiming to identify the source of these biases: dominance, inbreeding depression and/or an ill‐conditioned model due to the strong collinearity between YS, inbreeding and genetic trend. The study involved three maternal lines (A, V and H) and analysed two traits, total born (TB) and the number of kits at weaning (NW). Models fitting YS effect as fixed or random were implemented, in addition to additive genetic, permanent environment effects and non‐inbred dominance deviations effects. When YS was fitted as a fixed effect, the genetic trends were overestimated compared to control populations, inbreeding had an apparent positive effect on litter size and the environmental trends were negative. When YS was fitted as random, the genetic trends were compatible with control populations results, inbreeding had a negative effect (lower prolificacy) and environmental trends were flat. The model fitting random YS, inbreeding and non‐inbred dominance deviations yielded the following ratios of additive and dominance variances to total variance for NW: 0.06 and 0.01 for line A, 0.06 and 0.00 for line V and 0.01 and 0.08 for line H. Except for line H, dominance deviations seem to be of low relevance. When it is confounded with inbreeding as in these lines, fitting YS effect as random allows correct estimation of genetic trends.
Does daily climate variation have an effect on species’ elevational range size?
Authors: Qian Hong , Field Richard , Zhang Jian , Zhang Yangjian
Published: July 2017

In their recent paper published in Science (2016, 351, 1437–1439), Chan et al. analysed 137 montane gradients, concluding that they found a novel pattern—a negative relationship between mean elevational range size of species and daily temperature variation, which was claimed as empirical evidence for a novel macrophysiological principle (Gilchrist's hypothesis). This intriguing possibility was their key conceptual contribution. Unfortunately, as we show, the empirical evidence was flawed because of errors in the analyses and substantial sampling bias in the data. First, we re‐ran their analyses using their data, finding that their model should have been rejected. Second, we performed two additional re‐analyses of their data, addressing biases and pseudoreplication in different ways, both times again rejecting the evidence claimed to support Gilchrist's hypothesis. These results overturn the key empirical findings of Chan et al.'s study. Therefore, the “macrophysiological principle” should be regarded as currently remaining unsupported by empirical evidence.
Nanoscopic analysis of oxygen segregation at tilt boundaries in silicon ingots using atom probe tomography combined with TEM and ab initio calculations
Authors: OHNO Y. , INOUE K. , FUJIWARA K. , KUTSUKAKE K. , DEURA M. , YONENAGA I. , EBISAWA N. , SHIMIZU Y. , INOUE K. , NAGAI Y. , YOSHIDA H. , TAKEDA S. , TANAKA S. , KOHYAMA M.
Published: July 2017

We have developed an analytical method to determine the segregation levels on the same tilt boundaries (TBs) at the same nanoscopic location by a joint use of atom probe tomography and scanning transmission electron microscopy, and discussed the mechanism of oxygen segregation at TBs in silicon ingots in terms of bond distortions around the TBs. The three‐dimensional distribution of oxygen atoms was determined at the typical small‐ and large‐angle TBs by atom probe tomography with a low impurity detection limit (0.01 at.% on a TB plane) simultaneously with high spatial resolution (about 0.4 nm). The three‐dimensional distribution was correlated with the atomic stress around the TBs; the stress at large‐angle TBs was estimated by ab initio calculations based on atomic resolution scanning transmission electron microscopy data and that at small‐angle TBs were calculated with the elastic theory based on dark‐field transmission electron microscopy data. Oxygen atoms would segregate at bond‐centred sites under tensile stress above about 2 GPa, so as to attain a more stable bonding network by reducing the local stress. The number of oxygen atoms segregating in a unit TB area NGB (in atoms nm−2) was determined to be proportional to both the number of the atomic sites under tensile stress in a unit TB area nbc and the average concentration of oxygen atoms around the TB [Oi] (in at.%) with NGB ∼ 50 nbc[Oi].