bluuebunny/crossref_metadata_2025 huggingface dataset:
Intellectual capital as enhancer of product novelty
Authors: Molodchik Mariia , Jardon Carlos Maria
Published: March 2017

Purpose

The purpose of this paper is to theoretically justify the link between the endowment of intellectual capital (IC) and product novelty, and to find empirical evidence for such a link for small and medium-sized enterprises (SMEs) in the Russian business environment.

Design/methodology/approach

The study implements an intellectual capital-based view and the concept of novelty proposed by Schumpeter to highlight the crucial role of knowledge for transition to a higher level of competition. Drawing on a literature review, the authors determine three specific components of IC: foreign human capital, information and communication technology (ICT) capital developed at an international level and cooperation with foreign partners in order to pinpoint a premier position on the next level of the market. For empirical testing of the proposed model, a data set comprising more than 1,400 Russian manufacturing SMEs was used. Estimations were performed with the help of a principal component analysis and ordinal logistic regression.

Findings

The findings reveal that higher (IC) endowment promotes the level of product novelty. For Russian manufacturing SMEs, the most important is R&D capital. At the same time, ICT capital developed at an international level and cooperation with foreign partners contribute significantly to the probability of transition to a new market level.

Research limitations/implications

The study employs cross-sectional data that restrict the analysis of innovation dynamics.

Practical implications

The study appears to have policy implications for the development of governmental programmes for Russian SMEs such as the creation of IC awareness, training for IC management, special programmes for R&D support and ICT capital accumulation.

Originality/value

This paper proposes a new approach for investigating the “knowledge-innovation” link, shifting the focus from a general analysis of product innovation to a level of novelty for product innovation. This is the first empirical study of the relationship between IC components and the level of product novelty for SMEs in the context of the Russian business environment.
Applying the high performance organisation framework in the horticulture and greenhouse sector
Authors: de Waal André , Meingast Alex
Published: March 2017

Purpose

The Dutch agricultural sector nowadays experiences many challenges. To deal with these, the sector has been interested in finding ways to improve performance. Mostly, the improvement research has concentrated in the areas of innovation of products and quality, supply chain management, cooperatives, entrepreneurship and human resources. However, hardly any research has been done into ways to strengthen the internal organisation, encompassing the quality of management, employees and processes and systems of the agriculture company. This paper aims to address this research gap by evaluating whether the high performance organisation (HPO) framework, a scientific validated analysis and improvement technique, can be used to help agricultural enterprises to strengthen their internal organisation.

Design/methodology/approach

The HPO Questionnaire was applied at four Dutch horticulture companies to evaluate their performance. Subsequently, at each company, interviews were held to obtain more information about the scores. Then, a workshop was organised with the management of all four companies to discuss the study results.

Findings

The workshop showed that the framework was suitable for the participating companies to start improving their organisations, as management of all four companies agreed that the analysis and recommendations, derived from analysing the questionnaire data and the interviews, were highly relevant to their business.

Originality/value

As there is no holistic organisational evaluation and improvement technique which looks specifically at the internal organisation of horticulture companies, available for the agricultural sector, the application of the HPO Framework in this sector is the first of its kind.
Corporate entrepreneurship and market performance
Authors: Jancenelle Vivien E. , Storrud-Barnes Susan , Javalgi Rajshekhar (Raj) G.
Published: March 2017

Purpose

The purpose of this paper is to investigate the effects of a firm’s entrepreneurial proclivity on market performance for large, publicly traded US firms. This study draws upon the five-dimensional view of corporate entrepreneurship (CE) and develops hypotheses aimed at understanding the effects of direct effect of CE cues of proactiveness, autonomy, innovativeness, competitive aggressiveness and risk-taking on stock performance during earnings conference calls.

Design/methodology/approach

The entrepreneurial orientation of 339 firm post-earnings announcement conference calls is analyzed through a content analysis of transcripts, and the impact of CE cues on stock price is measured using event-study methodology.

Findings

The results suggest that the cueing the CE dimensions of innovativeness, risk-taking and especially autonomy have a positive effect on market performance during conference calls, while competitive aggressiveness has a negative effect. No effect was found for proactiveness.

Research limitations/implications

The effect of entrepreneurial proclivity on firm value is not uniform. Not all dimensions of CE have a positive effect on market performance at a corporate level, and measuring each dimension of CE separately may be a valuable approach for future research.

Practical implications

Firms may create more value when they cue specific entrepreneurial attributes, and cueing competitive aggressiveness may not be desirable.

Originality/value

This study fills a gap in the literature by measuring the direct effect of CE cues on market performance through an innovative research design which relies on computer-aided text analysis.
Case of bullous pemphigoid coexisting with anti‐desmoglein autoantibodies
Authors: Tie Duerna , Yoshida Tokiko , Chinuki Yuko , Da Xia , Ishikawa Noriyoshi , Morita Eishin
Published: March 2017

A 79‐year‐old Japanese woman had clinical and histopathological features of bullous pemphigoid, while direct immunofluorescence test revealed C3 and immunoglobulin G depositions in the lower cell surfaces of the epidermis in addition to those in the dermoepidermal junction. Chemiluminescent enzyme immunoassays were positive for desmoglein‐1 and ‐3 antibodies in addition to anti‐BP180 antibodies. In an immunoblotting study, antibodies against both 180‐kDa bullous pemphigoid antigen and 130‐kDa pemphigus vulgaris antigen were detected. Based on these results, bullous pemphigoid coexisting with anti‐desmoglein autoantibodies was diagnosed in this case.
Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod
Authors: Oyama Satomi , Funasaka Yoko , Tsuchiya Shin‐ichi , Kawana Seiji , Saeki Hidehisa
Published: March 2017

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll‐like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non‐melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo‐network (“strawberry”) pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki‐67‐positive proliferative cells in the epidermis was decreased and that of CD117‐positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.
Critical contribution of the interleukin‐6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis
Authors: Taniguchi Takashi , Asano Yoshihide , Fukasawa Takemichi , Yoshizaki Ayumi , Sato Shinichi
Published: March 2017

Reflecting the critical role of interleukin (IL)‐6 in systemic sclerosis (SSc), tocilizumab, an anti‐IL‐6 receptor antibody, is currently under a global phase III trial against skin sclerosis of this disease. We here demonstrate that the IL‐6/signal transducer and activator of transcription 3 axis is broadly activated in various cell types in the lesional skin of SSc patients irrespective of disease subtypes, especially in endothelial cells. Importantly, 12 monthly infusions of tocilizumab improved nailfold capillary changes as well as skin sclerosis in a patient with diffuse cutaneous SSc. The present findings suggest a potential disease‐modifying effect of tocilizumab on SSc vasculopathy.
Hypohidrosis and metal allergy: Trigger factors for unilateral lichen planus
Authors: Fukumoto Takeshi , Tsuchiyama Shinji , Fukunaga Atsushi , Nishigori Chikako
Published: March 2017

Unilateral lichen planus (LP) is a rare clinical variant of LP. The etiology of unilateral LP has not been clarified, although various causes have been reported because of the characteristic distribution. We focused on the contribution of metal allergy and sweating in the development of unilateral LP in this case. To confirm the presence of metal allergy, patch tests with metal allergens were performed. To investigate the cause of the unilateral distribution in unilateral LP, the function of sweating and sweat leaking in the dermis was assessed by a thermoregulatory sweat test and immunohistochemical staining of dermcidin. The patch tests with SnCl2, H2PtCl6, ZnCl2 and MnCl2 were positive. The thermoregulatory sweat test using the starch–iodine method (Minor test) with sweating provoked by heat stimulation revealed hypohidrosis of the affected area, whereas no skin lesions were observed on the dorsal hand and wrist where sweating was normal. Histopathological examination showed keratin plugging of the acrosyringium and lymphocytic infiltrations in the papillary and subpapillary dermis around the intraepidermal and intradermal eccrine duct in the affected area. The immunohistochemical staining of dermcidin confirmed sweat leakage in the subpapillary dermis in the affected area. The symptoms refractory to the topical steroids were markedly improved after removal of the dental metals. The coexistence of metal allergy and sweat leakage in the hypohidrotic area may be involved in the development of unilateral LP.
Robust dual‐sensor data sea‐surface ghost attenuation for quality control purposes
Authors: Caprioli Philippe , Ferber Ralf
Published: March 2017

Three‐dimensional receiver ghost attenuation (deghosting) of dual‐sensor towed‐streamer data is straightforward, in principle. In its simplest form, it requires applying a three‐dimensional frequency–wavenumber filter to the vertical component of the particle motion data to correct for the amplitude reduction on the vertical component of non‐normal incidence plane waves before combining with the pressure data. More elaborate techniques use three‐dimensional filters to both components before summation, for example, for ghost wavelet dephasing and mitigation of noise of different strengths on the individual components in optimum deghosting. The problem with all these techniques is, of course, that it is usually impossible to transform the data into the crossline wavenumber domain because of aliasing. Hence, usually, a two‐dimensional version of deghosting is applied to the data in the frequency–inline wavenumber domain. We investigate going down the “dimensionality ladder” one more step to a one‐dimensional weighted summation of the records of the collocated sensors to create an approximate deghosting procedure. We specifically consider amplitude‐balancing weights computed via a standard automatic gain control before summation, reminiscent of a diversity stack of the dual‐sensor recordings. This technique is independent of the actual streamer depth and insensitive to variations in the sea‐surface reflection coefficient. The automatic gain control weights serve two purposes: (i) to approximately correct for the geometric amplitude loss of the Z data and (ii) to mitigate noise strength variations on the two components. Here, Z denotes the vertical component of the velocity of particle motion scaled by the seismic impedance of the near‐sensor water volume. The weights are time‐varying and can also be made frequency‐band dependent, adapting better to frequency variations of the noise. The investigated process is a very robust, almost fully hands‐off, approximate three‐dimensional deghosting step for dual‐sensor data, requiring no spatial filtering and no explicit estimates of noise power. We argue that this technique performs well in terms of ghost attenuation (albeit, not exact ghost removal) and balancing the signal‐to‐noise ratio in the output data. For instances where full three‐dimensional receiver deghosting is the final product, the proposed technique is appropriate for efficient quality control of the data acquired and in aiding the parameterisation of the subsequent deghosting processing.
Light Rail, Land Values and Taxes
Authors: Murray Cameron K.
Published: March 2017

Land value gains attributable to the light rail system in Gold Coast, Australia, are estimated. Using a panel of statutory land valuations, a model of location‐specific gains allowing for price effects at multiple distances from stations across time is estimated. Total value gains to nearby landowners are in the range $240–$314 million, around a quarter of the project's capital cost. Scope to fund transport investment from value gains is apparent, and the city council and the state government have the administrative structures to recoup funds from benefiting landowners. Exemptions and budgeting practices mean little is recouped in practice.
Effects of Fermented Edible Seeds and Their Products on Human Health: Bioactive Components and Bioactivities
Authors: Gan Ren‐You , Li Hua‐Bin , Gunaratne Anil , Sui Zhong‐Quan , Corke Harold
Published: March 2017

There is a long history of using fermentation in food production. Edible seeds, such as certain beans and cereal grains, are important in the human diet and provide many health benefits. Various microbes, such as lactic acid bacteria, molds, and yeasts, considered as generally recognized as safe (GRAS) microbes, are commonly used to ferment edible seeds and their products. Fermentation can change bioactive components and produce new bioactivities. In order to highlight the importance of fermentation on bioactive components and bioactivities in edible seeds, this review, therefore, summarizes recent relevant studies and discusses fermentation procedures and influences of fermentation on their bioactive components and bioactivities. Overall, fermented edible seeds and their products contain enhanced bioactive components, especially γ‐aminobutyric acid and natural phenolics, and they possess versatile bioactivities, such as antioxidant and anti‐cancer effects, and, therefore, can be recommended as an important part of the human diet, or they can be developed into functional foods to help in the prevention of certain chronic diseases.
Influence of Extrusion Cooking on In Vitro Digestibility, Physical and Sensory Properties of Brazilian Pine Seeds Flour (Araucaria Angustifolia)
Authors: Boff Zortéa‐Guidolin Manoela Estefânea , Piler de Carvalho Carlos Wanderlei , Bueno de Godoy Rossana Catie , Mottin Demiate Ivo , Paula Scheer Agnes
Published: March 2017

Brazilian pine seeds (pinhão) are gluten‐free products derived from Araucaria angustifolia. The commercialization of these seeds is essentially associated with a low level of industrialization. In this context, extrusion cooking is a potential alternative for preparing extrudates of pinhão as a food product, which can be easily digested and is ready for human consumption. Brazilian pine seeds flour was processed in a single‐screw extruder following a central composite rotatable design. Three factors (independent parameters) were considered: moisture content (14 to 22 g/100 g), screw speed (100 to 250 rpm), and temperature in the 3rd heating zone (120 to 200 °C). The structural characteristics, in vitro digestibility and sensory acceptance were also evaluated. The resistant starch contents is almost reduced to zero after extrusion cooking while the slowly digestible starch content is increased. An increase in moisture positively affected the hardness and the luminosity (L*), although it negatively affected the volumetric expansion index, crispness, and color parameters (a*, b*, and ΔE). The experimental conditions of this study allowed the production of expanded extrudates from Brazilian pine seeds with good expansion, texture properties, and acceptance qualities. Thus, extrusion cooking was found to be a potential method for the industrialization of Brazilian pine seeds as a food product.
Preparation and Oxidation Stability Evaluation of Tea Polyphenols‐Loaded Inverse Micro‐Emulsion
Authors: Lan Xiaohong , Sun Jingjing , Yang Ying , Chen Mengjie , Liu Jianhua , Wu Jinhong , Wang Zhengwu
Published: March 2017

Compared to synthetic antioxidants, tea polyphenols (TPs) has its own advantages in edible oil industry, however, the hydrophilic properties have restricted its applications. In this study, the ternary phase diagram of TPs‐loaded micro‐emulsion (ME) system was constructed, in which glyceryl monooleate (GMO), Tween80, linoleic acid as the surfactants, ethanol as the co‐surfactant and soybean, corn, sunflower oil as the oil phase, have been used for the preparation of ME. The results indicated that a composition of ME (57.5% oil, 18% Tween80, 18% GMO, 4% Linolic acid, and 2.5% water+ethanol) could dissolve maximum water and could stable for 2 mo at room temperature with an average diameter of 6 to 7 nm, as detected by means of dynamic light scattering (DLS). The loaded of TPs into ME led to an increase of particle size to 15 to 16 nm, due to increased polarity of the water phase. The antioxidant capacity of TPs in ME was characterized by the peroxide value (POV) method. The addition of 1% water phase with 0.1 g/mL TPs could retain the POV at low value for 30 d at accelerating temperature 50 °C. Meanwhile, comparing the three edible oil, ME with corn oil has lower conductivity and higher value of POV during the storage. This work provides an efficient and environmentally friendly approach for the preparation of TPs‐loaded ME, which is beneficial to the application of TPs in edible oil.
Will your paper be used in a meta‐analysis? Make the reach of your research broader and longer lasting
Authors: Gerstner Katharina , Moreno‐Mateos David , Gurevitch Jessica , Beckmann Michael , Kambach Stephan , Jones Holly P. , Seppelt Ralf
Published: March 2017

Ecological and evolutionary research increasingly uses quantitative synthesis of primary research studies (meta‐analysis) for answering fundamental questions, informing environmental policy and summarizing results for decision makers.

Knowing how meta‐analysis works is important for researchers so that their research can have broader impact. Meta‐analytic thinking encourages scientists to see single primary research studies as substantial contributions to a larger picture.

To facilitate inclusion in a meta‐analysis, relevant primary research studies must be found and basic information about the methods and results must be thoroughly, clearly and transparently reported. While many published papers provide this information, it is common for essential data to be omitted, leading to study exclusion from meta‐analyses.

We provide guidelines for correctly reporting basic data needed from primary studies in ecology and evolutionary biology so that they can be included in meta‐analyses, together with examples that show how data should be reported to enable calculation and analysis of effect sizes, and how data should be made accessible.

These guidelines are important for reporting research results in general, whether or not results are included in subsequent meta‐analyses, because they are necessary for the interpretation and assessment of study outcomes. Increased implementation of these guidelines by authors, editors and publishers, and reinforcement by funders, will foster higher quality and more inclusive syntheses, further the goals of transparency and reproducibility in science, and improve the quality and value of primary research studies.
Lost in parameter space: a road map for stacks
Authors: Paris Josephine R. , Stevens Jamie R. , Catchen Julian M.
Published: March 2017

Restriction site‐Associated DNA sequencing (RAD‐seq) has become a widely adopted method for genotyping populations of model and non‐model organisms. Generating a reliable set of loci for downstream analysis requires appropriate use of bioinformatics software, such as the program stacks.

Using three empirical RAD‐seq datasets, we demonstrate a method for optimising a de novo assembly of loci using stacks. By iterating values of the program's main parameters and plotting resultant core metrics for visualisation, researchers can gain a much better understanding of their dataset and select an optimal set of parameters; we present the 80% rule as a generally effective method to select the core parameters for stacks.

Visualisation of the metrics plotted for the three RAD‐seq datasets shows that they differ in the optimal parameters that should be used to maximise the amount of available biological information. We also demonstrate that building loci de novo and then integrating alignment positions is more effective than aligning raw reads directly to a reference genome.

Our methods will help the community in honing the analytical skills necessary to accurately assemble a RAD‐seq dataset.
Nonmydriatic Fundoscopic Imaging Using the Pan Optic iExaminer System in the Pediatric Emergency Department
Authors: Day Lindsay M. , Wang Serena X. , Huang Craig J.
Published: March 2017

Objectives

The primary objective of this study was to determine the percentage of clinically adequate (CA) fundoscopic images that could be obtained using the Pan Optic iExaminer system to perform nonmydriatic fundoscopic imaging in the pediatric emergency department (ED). Secondary objectives were to identify target age groups in which this technology is best utilized and evaluate the overall ease of use in this setting.

Methods

Children 18 years of age or less who presented to the pediatric ED with a non–eye‐related chief complaint were enrolled and stratified by age group (0–2, 2–6, and 6–18 years). Each enrolled patient underwent a bilateral eye examination using the Pan Optic iExaminer system. Images were submitted for review to a pediatric ophthalmologist and were graded based on clarity and field of view. Ease of use was defined as 80% of patients having at least one image of quality to be considered “clinically adequate” for obtaining a full view of the optic nerve, examination time for both eyes 15 minutes or less, and three attempts or less for each eye.

Results

Overall, 91.06% (95% confidence interval [CI] = 86.01% to 96.1%) of children ages 2–18 years had at least one CA image obtained. A total of 16% (95% CI = 7% to 26%) of children 0–2 years, 85% (95% CI = 76% to 94.15%) of children 2–6 years, and 9% (95% CI = 92% to 100%) of 6–18 years had at least one CA image. The median total examination time was 3 minutes 24 seconds (interquartile range = 2 minutes 27 seconds to 4 minutes 49 seconds).

Conclusion

Fundoscopic images were consistently obtained using the Pan Optic iExaminer system in the pediatric ED particularly in children 2–18 years of age. CA images were obtained in children less than 2 years old, but less consistently.
Intravenous Versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Alshehri Abdussalam , Abulaban Ahmad , Bokhari Rakan , Kojan Suleiman , Alsalamah Majid , Ferwana Mazen , Murad Mohammad Hassan
Published: March 2017

Background

The acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity.

Objective

The objective was to assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non‐IV BDZ efficacy in the real world with regard to failure rates (primary outcome), interval to seizure control, and observed complications (secondary outcomes).

Methods

A systematic review was performed using Medline, Embase, and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi‐randomized controlled trials directly comparing IV to non‐IV (buccal, rectal, intranasal, or intramuscular) BDZ were included.

Results

Our search strategy retrieved 2,604 citations for review. A total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non‐IV BDZ was superior to IV BDZ (odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56–0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74–1.81). Non‐IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69–5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52–0.95 minutes). Respiratory complications requiring intervention were similar between non‐IV BDZ and IV BDZ, regardless of administration route (risk difference = 0.00; 95% CI = –0.02 to 0.01).

Conclusion

Non‐IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher‐quality studies and further evaluation in different age groups are warranted.
Effects of ovarian structures identified at Ovsynch™ enrolment, disease history and lactation variables on odds of pregnancy to a fixed‐time artificial insemination after Ovsynch™
Authors: Ingenhoff L , Hall E , Ranjbar NI S , House JK
Published: March 2017

Objective

To determine the effects of ovarian structures present at Ovsynch™ enrolment, disease history, lactation variables and times bred on pregnancy per fixed‐time artificial insemination (FTAI) following fixed‐time insemination after Ovsynch and to determine the relationship between the size of ovarian follicular structures and concurrent presence of a corpus luteum (CL).

Methods

The study was conducted in a 3000‐cow Holstein dairy herd. Over a 6‐month period, 886 non‐pregnant cows were examined by transrectal ultrasound and enrolled into 1132 Ovsynch events. Enrolled cows were synchronised using an Ovsynch‐56 protocol. At enrolment, both ovaries were scanned by transrectal ultrasound to identify and record the presence and size of ovarian structures. Cows that did not return to oestrus were pregnancy tested 32–38 days post‐insemination. Univariable and multivariable generalised linear mixed models (GLMMs) were used to determine the effect of each variable on pregnancy per FTAI. A univariable GLMM was also used to analyse the relationship between size of the dominant follicular structure and concurrent presence of a CL.

Results

CL size (P = 0.039) and presence of a luteal cyst (P = 0.002) at Ovsynch enrolment significantly increased the odds of pregnancy. Occurrence of lameness (P = 0.035) or mastitis (P = 0.008) between calving and enrolment significantly decreased the odds of pregnancy. Neither the presence nor size of a follicular structure significantly affected the odds of pregnancy, although cows with larger follicular structures were less likely to have a concurrent CL (P < 0.001).

Conclusion

Presence of luteal tissue at Ovsynch enrolment and recent disease events affected pregnancy per FTAI in cows inseminated after Ovsynch.
Carfilzomib induces leukaemia cell apoptosis via inhibitingELK1/KIAA1524 (Elk‐1/CIP2A) and activatingPP2A not related to proteasome inhibition
Authors: Liu Chun‐Yu , Hsieh Feng‐Shu , Chu Pei‐Yi , Tsai Wen‐Chun , Huang Chun‐Teng , Yu Yuan‐Bin , Huang Tzu‐Ting , Ko Po‐Shen , Hung Man‐Hsin , Wang Wan‐Lun , Shiau Chung‐Wai , Chen Kuen‐Feng
Published: March 2017

Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti‐leukaemic strategy.KIAA1524 (also termedCIP2A), an oncoprotein inhibitingPP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated withKIAA1524 protein downregulation, increasedPP2A activity and decreased p‐Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression ofKIAA1524, or pretreatment with thePP2A inhibitor, okadaic acid, suppressed carfilzomib‐induced apoptosis andKIAA1524 downregulation in sensitive cells, whereas co‐treatment with thePP2A agonist, forskolin, enhanced carfilzomib‐induced apoptosis in resistant cells. Mechanistically, carfilzomib affectedKIAA1524transcription through disturbingELK1 (Elk‐1) binding to theKIAA1524promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib onKIAA1524 and p‐Akt expression, as well asPP2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication ofKIAA1524 in leukaemia treatment.
Pathogenesis and management of antiphospholipid syndrome
Authors: Arachchillage Deepa R.J. , Laffan Mike
Published: March 2017

Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the ‘antiphospholipid syndrome’ (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I‐specific anti‐β2‐glycoprotein‐I antibodies. This in turn has pointed to endothelial and complement activation as important factors in the pathogenesis of APS. Consequently, although anticoagulation remains the standard treatment for thrombotic APS and during pregnancy, the realisation that these additional pathways are involved in the pathogenesis of APS has significant implications for treatment: agents acting outside the coagulation system, such as hydroxychloroquine for pregnancy complications and sirolimus as an inhibitor of the mammalian target of rapamycin (mTOR) pathway, are now under evaluation and represent a radical change in thinking for haematologists. Conventional anticoagulation is also under challenge from new, direct acting anticoagulants. This review will provide a comprehensive overview of the evolving understanding of APS pathogenesis and how this and novel therapeutics will alter diagnosis and management.
Middle Pleistocene ice‐marginal sedimentation in the transitional zone between the constrained and unconstrained ice‐sheet margin, East Anglia, England
Authors: Leszczynska Karolina , Boreham Steve , Gibbard Philip L.
Published: March 2017

It is uncommon in the North Sea basin and northwestern Europe for the ice‐marginal glacial successions of the Middle Pleistocene, Anglian (Elsterian) age to be well preserved and not overridden by subsequent glaciations. The existence of extensive and thick (˜20 m) Middle Pleistocene sand and gravel successions in East Anglia, England, provide a unique opportunity to reconstruct and understand the palaeoenvironmental conditions in the Anglian ice‐marginal zone, and further across the North Sea basin. This paper uses data from 80 sections in two sand and gravel quarries in East Anglia to provide the first evidence concerning: (i) the character of the ice‐marginal processes in the unique, transitional zone between the topographically constrained and unconstrained Anglian ice‐sheet margin; (ii) the role of meltwater in the re‐shaping of topographically driven preglacial drainage; and (iii) the position and the number of oscillations of the Anglian ice‐sheet margin in the form of a sediment‐landform assemblage. Moreover the current research adds to the discussion on the presence and extent of the proglacial lake in the North Sea Basin during the Anglian glaciation. The sand and gravel successions in the Anglian ice‐marginal zone are primarily reworked proto‐Thames sediments deposited by meltwater. At the beginning of the glaciation, the meltwater followed the preglacial (proto‐Thames) river course. However, as the ice sheet advanced, it was re‐routed, overwhelming and abandoning the old river course and depositing an extensive ice‐marginal subaqueous fan. The succession includes evidence for at least two enhanced meltwater release events, as well as indications of glaciolacustrine sedimentation. The character of the described sedimentary settings is discussed in the wider context of the presence of the North Sea Lake.
Reflecting on what ‘you said’ as a way of reintroducing difficult topics in child mental health assessments
Authors: Kiyimba Nikki , O'Reilly Michelle
Published: March 2017

Background

In child and adolescent mental health assessments, questions are integral to the process. There has been limited research focused on the assessment process, or on how questions are constructed within this clinical environment.

Methods

We examined 28 naturally occurring initial assessments, with particular attention to how practitioners used questions in their communication with children and young people. We utilised conversation analysis to examine the data.

Results

Analysis revealed a particular type of question preface used to reintroduce a prior topic. This was achieved through the use of ‘you said x’ as a foundation for asking a follow‐up question and demonstrated active listening.

Conclusions

Arguably, this approach is a useful way of gathering assessment‐relevant information in a child‐centred way.
Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study
Authors: Yamazaki Naoya , Kiyohara Yoshio , Uhara Hisashi , Uehara Jiro , Fujimoto Manabu , Takenouchi Tatsuya , Otsuka Masaki , Uchi Hiroshi , Ihn Hironobu , Minami Hironobu
Published: March 2017

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 (PD‐1) ligands. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single‐arm, open‐label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee‐assessed overall response rate was 34.8% (90% confidence interval, 20.8–51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment‐related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI‐142533.)
Ritonavir and ixazomib kill bladder cancer cells by causing ubiquitinated protein accumulation
Authors: Sato Akinori , Asano Takako , Okubo Kazuki , Isono Makoto , Asano Tomohiko
Published: March 2017

There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum stress is a novel approach to cancer treatment. The HIV protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate. The combination of ritonavir and ixazomib induced drastic apoptosis and inhibited the growth of bladder cancer cells synergistically. The combination decreased the expression of cyclin D1 and cyclin‐dependent kinase 4, and increased the sub‐G1 fraction significantly. Mechanistically, the combination caused ubiquitinated protein accumulation and endoplasmic reticulum stress. The combination‐induced apoptosis was markedly attenuated by the protein synthesis inhibitor cycloheximide, suggesting that the accumulation of ubiquitinated proteins played an important role in the combination's antineoplastic activity. Furthermore, the combination induced histone acetylation cooperatively and the decreased expression of histone deacetylases was thought to be one mechanism of this histone acetylation. The present study provides a theoretical basis for future development of novel ubiquitinated‐protein‐accumulation‐based therapies effective against bladder cancer.
Agreement and discrepancy between children, parents, and social workers on school‐based effort avoidance in child welfare services
Authors: Weber Hanna Maria , Petermann Franz , Rücker Stefan , Büttner Peter
Published: March 2017

A multiperspective approach is beneficial for obtaining reliable and multifaceted pictures of child behaviour problems. The goal of the present study is to examine interrater agreement on school‐based effort avoidance between children receiving child welfare services, parents, and social workers. Given previous findings, interrater agreement is expected to be low. Self‐reported data on school‐based effort avoidance were gathered for children and adolescents in child welfare services. Additionally, social workers (using the Teacher‐Report Checklist for social and learning behaviour) and parents (using the parallel version of the self‐rating questionnaire on school‐based effort avoidance) were asked to complete an external assessment tool to compare children's perspectives with the ratings of significant adults. The results confirmed significant discrepancies between parents' and children's ratings on effort avoidance tendencies. Furthermore, there were only small to moderate correlations between children's self‐ratings and the adults' assessments; however, the consensus between adults was higher than the interrater agreement between children and social workers. Discrepancies in ratings from multiple informants underline the importance of integrating multiple perspectives, especially children's perspectives, in the diagnostic process in order to plan and adapt appropriate care and treatment.
Markers of dietary protein intake are associated with successful weight loss in the POUNDS Lost trial
Authors: Bray G. A. , Ryan D. H. , Johnson W. , Champagne C. M. , Johnson C. M. , Rood J. , Williamson D. A. , Sacks F. M.
Published: March 2017

To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24‐h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m−2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (−4.4 kg [95% CI: −5.9, −3.0]) than for women in the lowest carbohydrate group (−1.8 kg [95% CI: −3.2, −0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow‐up protein intake was associated with greater weight loss, consistent with the ‘protein spread theory’. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months.
Cultural Differences in Visual Search for Geometric Figures
Authors: Ueda Yoshiyuki , Chen Lei , Kopecky Jonathon , Cramer Emily S. , Rensink Ronald A. , Meyer David E. , Kitayama Shinobu , Saiki Jun
Published: March 2017

While some studies suggest cultural differences in visual processing, others do not, possibly because the complexity of their tasks draws upon high‐level factors that could obscure such effects. To control for this, we examined cultural differences in visual search for geometric figures, a relatively simple task for which the underlying mechanisms are reasonably well known. We replicated earlier results showing that North Americans had a reliable search asymmetry for line length: Search for long among short lines was faster than vice versa. In contrast, Japanese participants showed no asymmetry. This difference did not appear to be affected by stimulus density. Other kinds of stimuli resulted in other patterns of asymmetry differences, suggesting that these are not due to factors such as analytic/holistic processing but are based instead on the target‐detection process. In particular, our results indicate that at least some cultural differences reflect different ways of processing early‐level features, possibly in response to environmental factors.
Development of a human cadaver model for training in laparoscopic donor nephrectomy
Authors: Sutton Erica R. H. , Billeter Adrian , Druen Devin , Roberts Henry , Rice Jonathan
Published: March 2017

Background

The organ procurement network recommends a surgeon record 15 cases as surgeon or assistant for laparoscopic donor nephrectomies (LDN) prior to independent practice. The literature suggests that the learning curve for improved perioperative and patient outcomes is closer to 35 cases. In this article, we describe our development of a model utilizing fresh tissue and objective, quantifiable endpoints to document surgical progress, and efficiency in each of the major steps involved in LDN.

Materials and Methods

Phase I of model development focused on the modifications necessary to maintain visualization for laparoscopic surgery in a human cadaver. Phase II tested proposed learner‐based metrics of procedural competency for multiport LDN by timing procedural steps of LDN in a novice learner.

Results

Phases I and II required 12 and nine cadavers, with a total of 35 kidneys utilized. The following metrics improved with trial number for multiport LDN: time taken for dissection of the gonadal vein, ureter, renal hilum, adrenal and lumbrical veins, simulated warm ischemic time (WIT), and operative time.

Conclusion

Human cadavers can be used for training in LDN as evidenced by improvements in timed learner‐based metrics. This simulation‐based model fills a gap in available training options for surgeons.
DO TERRORIST ATTACKS IMPACT EXCHANGE RATE BEHAVIOR? NEW INTERNATIONAL EVIDENCE
Authors: Narayan Paresh Kumar , Narayan Seema , Khademalomoom Siroos , Phan Dinh Hoang Bach
Published: March 2017

This study examines whether terrorist attacks affect bilateral exchange rates. Using historical 10‐minute exchange rate data for 21 countries' currency vis‐à‐vis the U.S. dollar, we show that exchange rate returns of all countries are statistically significantly affected by terrorist attacks. Some exchange rates appreciate and some depreciate following a terrorist attack, some currencies experience exchange rate reversals while others experience a persistent effect. Generally, the effect declines but persists as terrorist attacks become stale information. (JEL F31, F37)
Switching Aurora‐A kinase on and off at an allosteric site
Authors: Bayliss Richard , Burgess Selena G. , McIntyre Patrick J.
Published: March 2017

Protein kinases are central players in the regulation of cell cycle and signalling pathways. Their catalytic activities are strictly regulated through post‐translational modifications and protein–protein interactions that control switching between inactive and active states. These states have been studied extensively using protein crystallography, although the dynamic nature of protein kinases makes it difficult to capture all relevant states. Here, we describe two recent structures of Aurora‐A kinase that trap its active and inactive states. In both cases, Aurora‐A is trapped through interaction with a synthetic protein, either a single‐domain antibody that inhibits the kinase or a hydrocarbon‐stapled peptide that activates the kinase. These structures show how the distinct synthetic proteins target the same allosteric pocket with opposing effects on activity. These studies pave the way for the development of tools to probe these allosteric mechanisms in cells.