bluuebunny/crossref_metadata_2025 huggingface dataset:
Being moral and doing good to others
Authors: Septianto Felix , Soegianto Bambang
Published: February 2017

Purpose

Although previous research has established that moral emotion, moral judgment, and moral identity influence consumer intention to engage in prosocial behavior (e.g. donating, volunteering) under some circumstances, these factors, in reality, can concurrently influence judgment process. Therefore, it is important to get a more nuanced understanding of how the combinations of each factor can lead to a high intention to engage in prosocial behavior. The paper aims to discuss these issues.

Design/methodology/approach

This research employs fuzzy-set qualitative comparative analysis to explore different configurations of moral emotion, judgment, and identity that lead to a high consumer intention to engage in prosocial behavior.

Findings

Findings indicate four configurations of moral emotion, moral judgment, and moral identity that lead to a high intention to engage in prosocial behavior.

Research limitations/implications

This research focuses on the case of a hospital in Indonesia; thus, it is important not to overgeneralize the findings. Nonetheless, from a methodological standpoint, opportunity emerges to broaden the examinations in other service and cultural contexts.

Practical implications

The findings of this research can help the hospital to develop effective combinations of advertising and marketing strategies to promote prosocial behavior among its customers.

Originality/value

This paper provides the first empirical evidence on the existence of multiple pathways of moral emotion, judgment, and identity that lead to a high consumer intention to engage in prosocial behavior. The implications of this research also highlight the importance of cultural context in understanding consumer behavior.
Characterisation of direct 3D sand printing process for the production of sand cast mould tools
Authors: Hackney Philip Mark , Wooldridge Richard
Published: February 2017

Purpose

Metal casting industry is in recovery phase after the crisis in 2008; customer demand continues to increase, with 98.6 million metric tons cast in 2011. Traditional ferrous and non-ferrous casting techniques require one shot or permanent moulds which require tooling to produce. Tooling particularly for developmental projects can be costly and take valuable time to produce. Additive manufacturing (AM) has been used to manufacture sand patterns for metal sand casting using laser sintering and sand bonding. This research aims to focus on characterising the sand-bonded process developed by ExOne GmbhH Germany.

Design/methodology/approach

The approach taken in this research is to evaluate characteristics of parts built in the build volume for dimensional accuracy, tensile and compressive crush strength, density, impact strength and high temperature resistance. These properties are required to compare the 3D sand printing (3DSP) process to direct laser sand sintering (DLSS) and traditional Furan-based casting sand mixtures. The samples were taken from a production machine over a period of 30 days to ensure consistency.

Findings

The 3DSP process has the capability to manufacture sand patterns to an accuracy of ±0.5 mm or error less than 0.3 per cent; it has also demonstrated the best build position to achieve accurate parts. The research has demonstrated the 3DSP patterns are comparable to traditional methods for important casting material characteristics such as tensile, compression and impact strength. It has been shown that the 3DSP process is capable manufacturing significantly larger parts, with build production rates up to 30 times higher compared to similar parts manufactured via the DLSS process.

Research limitations/implications

As they has been very few 3DSP machines sold in Europe and particular UK, they has been little research into this new technique, and, therefore, they is a reliance on machine manufactures data for assessment. This research into 3DSP has increased the knowledge of this process significantly.

Practical implications

This research would be of interest to designers and manufacturing engineers wishing to take advantage of the implications of having new design freedom, tool less manufacturing with short lead times in a wide range of materials using fundamentally tried and tested century’s old casting techniques.

Originality/value

The research for this paper revealed very little published academic research in this area; therefore, this work will increase the body of knowledge for this niche AM process.
3D printing for continuous fiber reinforced thermoplastic composites: mechanism and performance
Authors: Yang Chuncheng , Tian Xiaoyong , Liu Tengfei , Cao Yi , Li Dichen
Published: February 2017

Purpose

Continuous fiber reinforced thermoplastic composites (CFRTPCs) are becoming more significant in industrial applications but are limited by the high cost of molds, the manufacturing boundedness of complex constructions and the inability of special fiber alignment. The purpose of this paper is to put forward a novel three-dimensional (3D) printing process for CFRTPCs to realize the low-cost rapid fabrication of complicated composite components.

Design/methodology/approach

For this purpose, the mechanism of the proposed process, which consists of the thermoplastic polymer melting, the continuous fiber hot-dipping and the impregnated composites extruding, was investigated. A 3D printing equipment for CFRTPCs with a novel composite extrusion head was developed, and some composite samples have been fabricated for several mechanical tests. Moreover, the interface performance was clarified with scanning electron microscopy images.

Findings

The results showed that the flexural strength and the tensile strength of these 10 Wt.% continuous carbon fiber (CCF)/acrylonitrile-butadiene-styrene (ABS) specimens were improved to 127 and 147 MPa, respectively, far greater than the one of ABS parts and close to the one of CCF/ABS (injection molding) with the same fiber content. Moreover, these test results also exposed the very low interlaminar shear strength (only 2.81 MPa) and the inferior interface performance. These results were explained by the weak meso/micro/nano scale interfaces in the 3D printed composite parts.

Originality/value

The 3D printing process for CFRTPCs with its controlled capabilities for the orientation and distribution of fiber has great potential for manufacturing of load-bearing composite parts in the industrial circle.
Investigation of concrete mixtures for additive construction
Authors: Rushing Todd S. , Al-Chaar Ghassan , Eick Brian Andrew , Burroughs Jedadiah , Shannon Jameson , Barna Lynette , Case Michael
Published: February 2017

Purpose

This paper aims to qualify traditional concrete mixtures for large-scale material extrusion in an automated, additive manufacturing process or additive construction.

Design/methodology/approach

A robust and viable automated additive construction process must be developed that has the capability to construct full-scale, habitable structures using materials that are readily available near the location of the construction site. Accordingly, the applicability of conventional concrete mixtures for large-scale material extrusion in an additive construction process was investigated. A qualitative test was proposed in which concrete mixtures were forced through a modified clay extruder and evaluated on performance and potential to be suitable for nozzle extrusion typical of additive construction, or 3D printing with concrete. The concrete mixtures were further subjected to the standard drop table test for flow, and the results for the two tests were compared. Finally, the concrete mixtures were tested for setting time, compressive strength and flexural strength as final indicators for usefulness in large-scale construction.

Findings

Conventional concrete mixtures, typically with a high percentage of coarse aggregate, were found to be unsuitable for additive construction application due to clogging in the extruder. However, reducing the amount of coarse aggregate provided concrete mixtures that were promising for additive construction while still using materials that are generally available worldwide.

Originality/value

Much of the work performed in additive manufacturing processes on a construction scale using concrete focuses on unconventional concrete mixtures using synthetic aggregates or no coarse aggregate at all. This paper shows that a concrete mixture using conventional materials can be suitable for material extrusion in additive construction. The use of conventional materials will reduce costs and allow for additive construction to be used worldwide.
Production of Ti-6Al-4V acetabular shell using selective laser melting: possible limitations in fabrication
Authors: Khorasani AmirMahyar , Gibson Ian , Goldberg Moshe , Littlefair Guy
Published: February 2017

Purpose

The purpose of this paper is to improve the manufacturing of a prosthetic acetabular shell by analyzing the main factors leading to failure during the selective laser melting (SLM) additive manufacturing (AM) process.

Design/methodology/approach

Different computer-aided design and computer-aided manufacturing processes have been applied to fabricate acetabular parts. Then, various investigations into surface quality, mechanical properties and microstructure have been carried out to scrutinize the possible limitations in fabrication.

Findings

Geometrical measurements showed 1.59 and 0.27 per cent differences between the designed and manufactured prototypes for inside and outside diameter, respectively. However, resulting studies showed that unstable surfaces, cracks, an interruption in powder delivery and low surface quality were the main problems that occurred during this process. These results indicate that SLM is an accurate and promising method for production of intricate shapes, provided that the appropriate settings of production conditions are considered to minimize possible limitations.

Originality/value

The contributions of this paper are discussions covering different issues in the AM fabrication of acetabular shells to improve the mechanical properties, quality and durability of the produced parts.
Activity model for homogenization of data sets in laser-based powder bed fusion
Authors: Feng Shaw C. , Witherell Paul , Ameta Gaurav , Kim Duck Bong
Published: February 2017

Purpose

Additive manufacturing (AM) processes are the integration of many different science and engineering-related disciplines, such as material metrology, design, process planning, in-situ and off-line measurements and controls. Major integration challenges arise because of the increasing complexity of AM systems and a lack of support among vendors for interoperability. The result is that data cannot be readily shared among the components of that system. In an attempt to better homogenization this data, this paper aims to provide a reference model for data sharing of the activities to be under-taken in the AM process, laser-based powder bed fusion (PBF).

Design/methodology/approach

The activity model identifies requirements for developing a process data model. The authors’ approach begins by formally decomposing the PBF processes using an activity-modeling methodology. The resulting activity model is a means to structure process-related PBF data and align that data with specific PBF sub-processes.

Findings

This model in this paper provides the means to understand the organization of process activities and sub-activities and the flows among them in AM PBF processes.

Research limitations/implications

The model is for modeling AM activities and data associated with these activity. Data modeling is not included in this work.

Social implications

After modeling the selected PBF process and its sub-processes as activities, the authors discuss requirements for developing the development of more advanced process data models. Such models will provide a common terminology and new process knowledge that improve data management from various stages in AM.

Originality/value

Fundamental challenges in sharing/reusing data among heterogeneous systems include the lack of common data structures, vocabulary management systems and data interoperability methods. In this paper, the authors investigate these challenges specifically as they relate to process information for PBF – how it is captured, represented, stored and accessed. To do this, they focus on using methodical, information-modeling techniques in the context of design, process planning, fabrication, inspection and quality control.
Fibroid vascularisation assessed with three‐dimensional power Doppler ultrasound is a predictor for uterine fibroid growth: a prospective cohort study
Authors: Nieuwenhuis LL , Keizer AL , Stoelinga B , Twisk JWR , Hehenkamp WJK , Brölmann HAM , Huirne JAF
Published: February 2017

Objective

To analyse fibroid vascularisation measured with three‐dimensional (3D) power Doppler in relation to absolute fibroid volume change during 12 months of follow up and in relation to fibroid growth rate per year.

Design

A prospective cohort study was performed between March 2012 and March 2014.

Setting

Outpatient clinic of the VU medical centre, Amsterdam.

Population or sample

All premenopausal women diagnosed with a maximum of two fibroids with expectant management were consecutively included.

Methods

Three‐dimensional ultrasound including power Doppler was performed at baseline, 3, 6 and 12 months. Volume and vascular parameters were calculated using VOCAL software.

Main outcome measures

The relationship between vascular index (VI) at baseline and fibroid volume over time was analysed using linear mixed model analyses for repeated measurements. Second, the relationship between VI at baseline and fibroid growth rate per year was calculated using linear regression analyses. Analyses were adjusted for possible confounders.

Results

In all, 66 women (mean age 42 years) completed 12 months of follow up without treatment. Baseline fibroid vascularisation (VI) measured with 3D power Doppler is correlated with fibroid volume at 12 months (P = 0.02 ). An increase of 1% in VI at baseline was associated with a 7.00‐cm3 larger fibroid volume at 12 months. Furthermore, vascularisation was also associated with fibroid growth rate per year (P = 0.04).

Conclusion

In women with uterine fibroids without therapy, baseline vascularisation (VI) measured with 3D power Doppler is correlated with absolute fibroid volume change at 12 months and with fibroid growth rate per year.

Tweetable abstract

Fibroid vascularisation correlates with absolute fibroid volume change and fibroid growth rate per year.
First record of the genus Codrus Panzer (Hymenoptera: Proctotrupidae) from South Korea with description of a new species
Authors: Park Bia , Kim Chang‐Jun , Lee Jong‐Wook
Published: February 2017

The genus Codrus Panzer, 1803 is recorded for the first time from South Korea. A new species and three newly recorded species are described: C. tripotini Lee and Park sp. nov., C. ciliatus Townes, 1981, C. nebriae (Watanabe, 1954) and C. niger Panzer, 1803. Additionally, C. ciliatus Townes is newly added to Chinese fauna. A key to the South Korean Codrus, diagnostic characteristics and photographs are provided.
Curcumin Protects Against Intestinal Origin Endotoxemia in Rat Liver Cirrhosis by Targeting PCSK9
Authors: Cai Yu , Lu Di , Zou Yanting , Zhou Chaohui , Liu Hongchun , Tu Chuantao , Li Feng , Liu Lili , Zhang Shuncai
Published: February 2017

Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl4)‐induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl4 subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl4‐induced cirrhosis rats. Enzyme‐linked immunosorbent assay (ELISA) and real‐time quantitative polymerase chain reaction (qRT‐PCR) showed that curcumin could reduce c‐reaction protein levels and inflammatory cytokine (TNF‐α, IL‐1β, IL‐6, and CINC‐1/IL‐8) concentrations in peripheral serum and liver tissue. Furthermore, curcumin treatment decreased lipopolysaccharide (LPS) levels in peripheral vein, but not in portal vein. As low‐density lipoprotein receptor (LDLR) is the important receptor on the surface of hepatocyte during LPS detoxification process, we used qRT‐PCR, western blot, and immunohistochemistry (IHC), finding that curcumin significantly increased LDLR protein levels, but not gene levels in the liver tissues. We also tested proprotein convertase subtilisin/kexin type 9 (PCSK9), one negative regulator of LDLR, by qRT‐PCR, western blot, and IHC. The results showed that PCSK9 significantly decreased both gene and protein levels in the rat liver tissues of curcumin treatment. Thus, we concluded that curcumin could function to protect against intestinal origin endotoxemia by inhibiting PCSK9 to promote LDLR expression, thereby enhancing LPS detoxification as one pathogen lipid through LDLR in the liver.
Egyptian tale from India: application of whole‐exome sequencing in diagnosis of atypical familial Mediterranean fever
Authors: Sandhya Pulukool , Vellarikkal Shamsudheen Karuthedath , Nair Aswin , Ravi Rowmika , Mathew John , Jayarajan Rijith , Kumar Anoop , Verma Ankit , Sivadas Ambily , Danda Debashish , Sivasubbu Sridhar , Scaria Vinod
Published: February 2017

Clinical diagnosis of autoinflammatory diseases requires a high degree of clinical suspicion and clinching molecular evidence to substantiate the diagnosis. This is more so in populations with low prevalence of these disorders. In this report, we describe the case of a young man from India with recurrent fever and persistent arthritis. The patient's forefathers were of Egyptian ancestry who practiced consanguinity. Molecular genetic analysis using whole‐exome sequencing suggested the presence of variants c.443A>T:p.E148V and c.442G>C:p.E148Q in the MEFV gene, earlier independently shown to be associated with familial Mediterranean fever (FMF) in a compound heterozygous state. The variants were further confirmed by capillary sequencing. This report also highlights the application of whole exome sequencing to delineate the allelic differences in the variants apart from serving as a quick genetic screening approach for autoinflammatory diseases. To the best of our knowledge, this is the first report of a compound heterozygosity for the two well‐characterized variants associated with atypical FMF in a patient.
The modelling spiral for solving ‘wicked’ environmental problems: guidance for stakeholder involvement and collaborative model development
Authors: Parrott Lael
Published: February 2017

Many problems in environmental management and sustainability have no single, optimal solution. Such problems are called ‘wicked problems’. Any solution to a wicked problem will significantly affect a wide range of stakeholders, and cannot be separated from human ethics, values and social equity. Experience with participatory approaches that include stakeholders shows that ecological modelling can lead to applied outcomes that may inform environmental management and policy, thus helping to solve wicked problems. However, many ecological models fail to meet this goal.

The key ways in which scientists and ecological modellers can contribute to the search for solutions to wicked problems in collaboration with stakeholders are described. Modelling is identified as a tool that scientists can bring into the deliberative process to facilitate dialogue and evidence‐based decision‐making within a stakeholder forum.

A modelling spiral is proposed as a framework for describing the stages of the modelling process leading to positive change in collaboration with stakeholders.

By following the recommendations of the modelling spiral, ecological modellers can accomplish socially relevant research that contributes to the collective search for sustainable solutions to wicked environmental problems.
Changes in the realized niche of the invasive succulent CAM plant Furcraea foetida
Authors: Barbosa Cristiana , Otalora Juan Manuel , Giehl Eduardo L. H. , Villalobos Fabricio , Loyola Rafael , Tessarolo Geiziane , Machado Nathália , Castellani Tânia Tarabini
Published: February 2017

Furcraea foetida (Asparagaceae) is a native plant of Central America and northern South America but there is no information about its country of origin. The species was introduced into Brazil and is now considered invasive, particularly in coastal ecosystems. To date, nothing is known about the environmental factors that constrain its distribution and there is only inconclusive information about its location of origin. We used reciprocal distribution models (RDM) to assess invasion risk of F. foetida across Brazil and to identify source regions in its native range. We also tested the niche conservatism hypothesis using Principal Components Analyses and statistical tests of niche equivalency and similarity between its native and invaded ranges. For RDM analysis, we built two models using maximum entropy, one using records in the native range to predict the invaded distribution (forward‐Ecological Niche Model or forward‐ENM) and one using records in the invaded range to predict the native distribution (reverse‐ENM). Forward‐ENM indicated invasion risk in the Cerrado region and the innermost region of the Atlantic Forest, however, failed to predict the current occurrence in southern Brazil. Reverse‐ENM supported an existing hypothesis that F. foetida originated in the Orinoco river basin, Amazon basin and Caribbean islands. Prediction errors in the RDM and multivariate analysis indicated that the species expanded its realized niche in Brazil. The niche similarity test further suggested that the niche differences are because of differences in habitat availability between the two ranges, not because of evolutionary changes. We hypothesize that physiological pre‐adaptation (especially, the crassulacean acid metabolism), human‐driven propagule pressure and high competitive ability are the main factors determining the current spatial distribution of the species in Brazil. Our study highlights the need to include F. foetida in plant invasion monitoring programs, especially in priority conservation areas where the species has still not been introduced.
Genomic prediction of reproduction traits for Merino sheep
Authors: Bolormaa S. , Brown D. J. , Swan A. A. , van der Werf J. H. J. , Hayes B. J. , Daetwyler H. D.
Published: February 2017

Economically important reproduction traits in sheep, such as number of lambs weaned and litter size, are expressed only in females and later in life after most selection decisions are made, which makes them ideal candidates for genomic selection. Accurate genomic predictions would lead to greater genetic gain for these traits by enabling accurate selection of young rams with high genetic merit. The aim of this study was to design and evaluate the accuracy of a genomic prediction method for female reproduction in sheep using daughter trait deviations (DTD) for sires and ewe phenotypes (when individual ewes were genotyped) for three reproduction traits: number of lambs born (NLB), litter size (LSIZE) and number of lambs weaned. Genomic best linear unbiased prediction (GBLUP), BayesR and pedigree BLUP analyses of the three reproduction traits measured on 5340 sheep (4503 ewes and 837 sires) with real and imputed genotypes for 510 174 SNPs were performed. The prediction of breeding values using both sire and ewe trait records was validated in Merino sheep. Prediction accuracy was evaluated by across sire family and random cross‐validations. Accuracies of genomic estimated breeding values (GEBVs) were assessed as the mean Pearson correlation adjusted by the accuracy of the input phenotypes. The addition of sire DTD into the prediction analysis resulted in higher accuracies compared with using only ewe records in genomic predictions or pedigree BLUP. Using GBLUP, the average accuracy based on the combined records (ewes and sire DTD) was 0.43 across traits, but the accuracies varied by trait and type of cross‐validations. The accuracies of GEBVs from random cross‐validations (range 0.17–0.61) were higher than were those from sire family cross‐validations (range 0.00–0.51). The GEBV accuracies of 0.41–0.54 for NLB and LSIZE based on the combined records were amongst the highest in the study. Although BayesR was not significantly different from GBLUP in prediction accuracy, it identified several candidate genes which are known to be associated with NLB and LSIZE. The approach provides a way to make use of all data available in genomic prediction for traits that have limited recording.
Health status, health behaviours and anxiety symptoms of older male caregivers: Findings from the Concord Health and Ageing in Men Project
Authors: Shu Chen‐Chun , Cumming Robert G , Kendig Hal L , Blyth Fiona M , Waite Louise M , Le Couteur David G , Handelsman David J , Naganathan Vasi
Published: February 2017

Objective

To explore differences between older male caregivers and non‐caregivers on health status, health behaviours and well‐being, including symptoms of anxiety.

Methods

Data were collected through self‐completed questionnaires and face‐to‐face interviews with 1705 community living men aged ≥70 in the Concord Health and Ageing in Men Project.

Results

Eleven per cent of older men were caregivers, of whom 81.7% were looking after their wives or partners. Older male caregivers did not have worse physical health or more depressive symptoms than non‐caregivers, but being a caregiver was associated with increased likelihood of reporting anxiety symptoms (OR: 2.32, 95% CI: 1.39–3.87). Caregivers had similar levels and frequencies of leisure activities but did more housework activities than non‐caregivers.

Conclusion

Higher anxiety levels were the main adverse health condition in older male caregivers. Strategies to assist minimising anxiety for caregivers should be a target of interventions.
Letter: multivariate clinical model for eosinophilic oesophagitis – is this generalisable to general population
Authors: Chitsaz E.
Published: February 2017

Linked Content

This article is linked to Von Arnim and Rohl et al papers. To view these articles visit https://doi.org/10.1111/apt.13869 and https://doi.org/10.1111/apt.13967.
Editorial: can we get more clinical benefit from thiopurine metabolite testing? Authors’ reply
Authors: Wong D. R. , Hooymans P. M.
Published: February 2017

Linked Content

This article is linked to Wong and Coenen et al and Fraser papers. To view these articles visit https://doi.org/10.1111/apt.13879 and https://doi.org/10.1111/apt.13942.
Editorial: relative efficacy of infliximab and adalimumab in Crohn's disease in an Australian and New Zealand cohort – authors’ reply
Authors: Radford‐Smith G. L. , Hartnell F. , Doecke J. D.
Published: February 2017

Linked Content

This article is linked to Doecke and Hartnell et al and Barreiro‐de Acosta and Gisbert papers. To view these articles visit https://doi.org/10.1111/apt.13880 and https://doi.org/10.1111/apt.13929.
Direct seeding of 16 Brazilian savanna trees: responses to seed burial, mulching and an invasive grass
Authors: Silva Raíssa R.P. , Vieira Daniel L.M.
Published: February 2017

Aims

To address whether seed and seedling functional traits have a significant effect on germination rates and seedling survival in direct‐seeding restoration efforts. We tested the hypotheses that: (1) seed burial only favours the emergence of round seeds; and (2) straw mulching improves soil moisture and prevents the emergence of the invasive grass Urochloa decumbens, promoting the establishment of native tree seedlings.

Location

Experimental field, Central Brazil. Savanna, recently dominated by exotic pasture.

Methods

We evaluated the effects of seed burial (surface and buried) and mulching (no‐mulch, 5‐cm straw mulch and 10‐cm straw mulch) on the emergence, survival and growth of 16 species of native Cerrado tree species with variable seed sizes and shapes and seedling types. Thirty seeds of each species were sown per treatment combination in three blocks.

Results

Seed burial did not affect the emergence of species with round seeds, but negatively affected species with flat seeds and phanerocotylar–epigeal–foliaceous seedlings. Straw mulching reduced the emergence of flat seeds and phanerocotylar seedlings, but increased soil moisture and strongly reduced U. decumbens emergence, resulting in a higher growth rate of tree seedlings up to 1 yr for five species.

Conclusion

Direct seeding is an effective technique to plant a mixture of Cerrado tree species for restoration, provided the soil is well prepared and there are mechanisms to control invasive species.
Efficacy and Tolerability of an Inhaled Selective Glucocorticoid Receptor Modulator – AZD5423 – in Chronic Obstructive Pulmonary Disease Patients: Phase II Study Results
Authors: Kuna Piotr , Aurivillius Magnus , Jorup Carin , Prothon Susanne , Taib Ziad , Edsbäcker Staffan
Published: February 2017

AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthma patients improved lung function and airway hyper‐reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double‐blind, randomized and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic patients with COPD (average pre‐bronchodilator forced expiratory volume in one‐second (FEV1) at screening was 50–52% of predicted normal). Pre‐bronchodilator FEV1 was primary variable, with other lung function parameters plus symptoms and 24‐hr plasma cortisol being secondary variables. Plasma concentrations of AZD5423 were also measured. Effects were compared against placebo and a reference glucocorticoid receptor agonist control. Neither AZD5423, at doses which have shown to be efficacious in allergen‐induced asthma, nor the reference control, at double the approved dose, had any clinically meaningful effect in the patient population studied in regard to lung function or markers of inflammation. Both GR modulators were well tolerated and did suppress 24‐hr cortisol. This study suggests that the selected population of patients with COPD does not respond to treatment with AZD5423 as regards lung function, while showing the expected systemic effects. It cannot be ruled out that a favourable lung function response of AZD5423 can be evoked using another experimental setting and/or within a different population of patients with COPD.
Bayesian Response-Adaptive Designs for Basket Trials
Authors: Ventz Steffen , Barry William T. , Parmigiani Giovanni , Trippa Lorenzo
Published: February 2017

We develop a general class of response-adaptive Bayesian designs using hierarchical models, and provide open source software to implement them. Our work is motivated by recent master protocols in oncology, where several treatments are investigated simultaneously in one or multiple disease types, and treatment efficacy is expected to vary across biomarker-defined subpopulations. Adaptive trials such as I-SPY-2 (Barker et al., 2009) and BATTLE (Zhou et al., 2008) are special cases within our framework. We discuss the application of our adaptive scheme to two distinct research goals. The first is to identify a biomarker subpopulation for which a therapy shows evidence of treatment efficacy, and to exclude other subpopulations for which such evidence does not exist. This leads to a subpopulation-finding design. The second is to identify, within biomarker-defined subpopulations, a set of cancer types for which an experimental therapy is superior to the standard-of-care. This goal leads to a subpopulation-stratified design. Using simulations constructed to faithfully represent ongoing cancer sequencing projects, we quantify the potential gains of our proposed designs relative to conventional non-adaptive designs.
Teacher structure as a predictor of students’ perceived competence and autonomous motivation: The moderating role of differentiated instruction
Authors: Guay Frédéric , Roy Amélie , Valois Pierre
Published: February 2017

Background

An important pedagogical practice is the provision of structure (Farkas & Grolnick, 2010, Motiv. Emot., 34, 266). According to self‐determination theory (SDT; Deci & Ryan, 1985, Intrinsic motivation and self‐determination in human behavior, Plenum, New York, NY), structure allows students to develop perceived competence in different school subjects, which in turn facilitates the development of autonomous motivation towards these subjects and limits the development of controlled motivation.

Aims

In this study, we test a mediated moderation model that posits that teacher structure has a stronger positive effect on students’ autonomous motivation (and a negative effect on controlled motivation) in French class when differentiated instruction is used, and that this moderation effect is mediated by perceived competence.

Sample

To test this model, we used a sample of 27 elementary school teachers and 422 students from Quebec, a province of Canada.

Methods

Data for teachers and students were collected with self‐report measures. The method used was a correlational one with a single measurement time.

Results

Results revealed that (1) the effect of teacher structure on students’ autonomous motivation was positive only when differentiated instruction strategies were frequently used, and this moderated effect was partially mediated by perceived competence, and (2) teacher structure was negatively associated with students’ controlled motivation only when differentiated instruction was provided infrequently, and this moderated effect was not explained by perceived competence.

Conclusions

These findings are discussed in the light of the literature on SDT and on differentiated instruction.
Impact of treatment variability on survival in immuno‐competent and immuno‐compromised patients with primary central nervous lymphoma
Authors: Karmali Reem , Nabhan Chadi , Petrich Adam M. , Raizer Jeffrey , Peace David , Lukas Rimas , Gordon Leo I. , Basu Sanjib , Chukkapalli Vineela , Venugopal Parameswaran
Published: February 2017

Patients with primary central nervous system lymphoma (PCNSL) treated in the ‘real‐world’ setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD‐MTX) regimen +/− rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/− systemic therapy). Fifty‐eight of 108 patients received rituximab. Twenty‐nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow‐up of 18·7 months, median overall survival (OS) was 65·2 months. In univariate analysis, HD‐MTX (median OS 72·7 vs. 2·7 months, P < 0·001) and rituximab (median not reached versus 28·4 months, P = 0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P = 0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno‐competent/compromised patients and similar to those achieved in recent clinical trials.
The assessment of knowledge and learning in competence spaces: The gain–loss model for dependent skills
Authors: Anselmi Pasquale , Stefanutti Luca , de Chiusole Debora , Robusto Egidio
Published: February 2017

The gain–loss model (GaLoM) is a formal model for assessing knowledge and learning. In its original formulation, the GaLoM assumes independence among the skills. Such an assumption is not reasonable in several domains, in which some preliminary knowledge is the foundation for other knowledge. This paper presents an extension of the GaLoM to the case in which the skills are not independent, and the dependence relation among them is described by a well‐graded competence space. The probability of mastering skill s at the pretest is conditional on the presence of all skills on which s depends. The probabilities of gaining or losing skill s when moving from pretest to posttest are conditional on the mastery of s at the pretest, and on the presence at the posttest of all skills on which s depends. Two formulations of the model are presented, in which the learning path is allowed to change from pretest to posttest or not. A simulation study shows that models based on the true competence space obtain a better fit than models based on false competence spaces, and are also characterized by a higher assessment accuracy. An empirical application shows that models based on pedagogically sound assumptions about the dependencies among the skills obtain a better fit than models assuming independence among the skills.
Sequence architecture and depositional evolution of the northern continental slope of the South China Sea: responses to tectonic processes and changes in sea level
Authors: Lin Changsong , Jiang Jing , Shi Hesheng , Zhang Zhongtao , Liu Jingyan , Qin Chenggang , Li Hao , Ran Huaijiang , Wei An , Tian Hongxun , Xing Zuochang , Yao Qingyu
Published: February 2017

The continental slopes of the South China Sea (SCS), the largest marginal sea on the continental shelf of Southeast Asia, are among the most significant shelf‐margin basins in the world because of their abundant petroleum resources and a developmental history related to sea floor spreading since Late Oligocene time. Based on integrated analyses of seismic, well‐logging and core data, we systematically document the sequence architecture and depositional evolution of the northern continental slope of theSCSand reveal its responses to tectonism, sea‐level change and sediment supply. The infill of this shelf‐margin basin can be divided into seven composite sequences (CS1–CS7) that are bounded by regional unconformities. Composite sequencesCS3 toCS7 have formed since Late Oligocene time, and each of them generally reflects a regional transgressive–regressive cycle. These large cycles can be further divided into 20 sequences that are defined by local unconformities or transgressive–regressive boundaries. Depositional–geomorphological systems represented on the continental slope mainly include shelf‐edge deltas, prodelta‐slope fans, clinoforms of the shelf‐margin slope, unidirectionally migrating slope channels, incised slope valleys, muddy slope fans, slope slump‐debris‐flow complexes and large‐scale soft‐sediment deformation of bedding. Changing sea levels, reflected by evidence from sequence architecture in the study area, are generally comparable with those of the Haq (1987) global sea level curve, whereas the regional transgressions and regressions were apparently controlled by tectonic uplift and subsidence. Composite sequencesCS3 andCS4 formed from Late Oligocene to Middle Miocene time and represent continental‐slope deposition during a time of northwest‐northeast seafloor spreading and subsequent development of sub‐basins in the southwest‐centralSCS. The development of composite sequencesCS5 toCS7 after Middle Miocene time was obviously influenced by the Dongsha Movement during convergence between theSCSand Philippine Sea plates. Climatic variations and monsoon intensification may have enhanced sediment supply during Late Oligocene‒Early Miocene (25–21 Ma) and Late Pliocene‒Pleistocene (3–0.8 Ma) times. This study indicates that shelf‐edge delta and associated slope fan systems are the most important oil/gas‐bearing reservoirs in theSCScontinental‐slope area.
Anti‐cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor‐positive breast cancer cells
Authors: Kurebayashi Junichi , Koike Yoshikazu , Ohta Yusuke , Saitoh Wataru , Yamashita Tetsumasa , Kanomata Naoki , Moriya Takuya
Published: February 2017

Estradiol (E2) increases not only the cell growth but also the cancer stem cell (CSC) proportion in estrogen receptor (ER)‐positive breast cancer cells. It has been suggested that the non‐canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER‐positive breast cancer cells. We studied anti‐CSC activity of a non‐canonical Hh inhibitor GANT61 in ER‐positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER‐positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD44/CD24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT61 with antiestrogens on the anti‐cell growth and anti‐CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER‐positive cell lines. E2 increased the expression levels of glioma‐associated oncogene (GLI) 1 and/or GLI2. GANT61 decreased the cell growth in association with a G1‐S cell cycle retardation and increased apoptosis. GANT61 decreased the E2‐induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2‐induced cell growth and CSC proportion. Combined treatments of GANT61 with antiestrogens additively enhanced anti‐cell growth and/or anti‐CSC activities in some ER‐positive cell lines. In conclusion, the non‐canonical Hh inhibitor GANT61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER‐positive breast cancer cells. GANT61 enhanced anti‐cell growth and/or anti‐CSC activities of antiestrogens in ER‐positive cell lines.
Short‐acting glucagon‐like peptide‐1 receptor agonists as add‐on to insulin therapy in type 1 diabetes: A review
Authors: Albèr Anders , Brønden Andreas , Knop Filip K.
Published: February 2017

A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well‐described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long‐acting GLP‐1RAs, but the risk–benefit ratio emerging from studies evaluating the effect of long‐acting GLP‐1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long‐acting GLP‐1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP‐1‐induced retardation of gastric emptying. In contrast, the short‐acting GLP‐1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short‐acting GLP‐1RAs are all derived from small open‐label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP‐1RAs, in particular short‐acting GLP‐1RAs, as add‐on to insulin in the treatment of type 1 diabetes.
Comparison of body mass index at diagnosis of diabetes in a multi‐ethnic population: A case‐control study with matched non‐diabetic controls
Authors: Paul Sanjoy K. , Owusu Adjah Ebenezer S. , Samanta Mayukh , Patel Kiran , Bellary Srikanth , Hanif Wasim , Khunti Kamlesh
Published: February 2017

Aims

To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non‐diabetic controls in a multi‐ethnic population.

Materials and methods

This was a case‐control study of 90 367 patients with incident diabetes and 362 548 age‐sex‐ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated.

Results

Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m2 at diagnosis (32.2 kg/m2) compared to the matched controls (27.4 kg/m2). White Europeans (n = 79 270), African‐Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m2, respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m2 (38%) than White Europeans (26%) and African‐Caribbeans (29%) (all
P
 < .01). Within the 18 to 70‐year age range, South Asian males and females had a significantly higher probability of developing diabetes in the continuously measured BMI range of 18 to 30 kg/m2, compared to White Europeans and African‐Caribbeans. Across all age groups <70 years, South Asians and African‐Caribbeans had a significantly higher probability of developing T2DM in the normal weight and overweight categories, compared to White Europeans. However, this risk pattern of developing diabetes was reversed amongst the obese in all age groups.

Conclusion

Risk patterns of developing diabetes at different levels of obesity varies among ethnic groups across all ages, while South Asians and African‐Caribbeans carry the highest risk at a younger age and at lower adiposity burden.
Unravelling intravertebral integration, modularity and disparity in Felidae (Mammalia)
Authors: Randau Marcela , Goswami Anjali
Published: February 2017

Morphological integration and modularity, which describe the relationships among morphological attributes and reflect genetic, developmental, and functional interactions, have been hypothesized to be major influences on trait responses to selection and thus morphological evolution. The mammalian presacral vertebral column shows little variation in vertebral count and therefore specialization for function occurs primarily through modification of vertebral shape. However, vertebral shape has been suggested to be under strong control from developmental canalization, although this has never been explicitly tested. Here, we assess hypotheses of developmental modules in the vertebrae of felids to determine whether developmental interactions are a primary influence on vertebral modularity. Additionally, we analyze the magnitudes of both intravertebral integration and disparity to evaluate if level of integration varies along the vertebral column and, if so, whether integration and disparity are associated. Our results confirm the hypothesis of vertebral developmental modularity, with most presacral vertebrae displaying two modules. Exceptions are concentrated in the boundaries among traditional and functional regions, suggesting that intravertebral modularity may reflect larger‐scale modularity of the felid vertebral column. We further demonstrate that overall integration and disparity are highest in posterior vertebrae, thus providing an empirical example of integration potentially promoting greater morphological responses to selection.