bluuebunny/crossref_metadata_2025 huggingface dataset:
Short DNA sequence patterns accurately identify broadly active human enhancers
Authors: Colbran Laura L. , Chen Ling , Capra John A.
Published: February 2017

Enhancers are DNA regulatory elements that influence gene expression. There is substantial diversity in enhancers’ activity patterns: some enhancers drive expression in a single cellular context, while others are active across many. Sequence characteristics, such as transcription factor (TF) binding motifs, influence the activity patterns of regulatory sequences; however, the regulatory logic through which specific sequences drive enhancer activity patterns is poorly understood. Recent analysis ofDrosophilaenhancers suggested that short dinucleotide repeat motifs (DRMs) are general enhancer sequence features that drive broad regulatory activity. However, it is not known whether the regulatory role of DRMs is conserved across species. We performed a comprehensive analysis of the relationship between short DNA sequence patterns, including DRMs, and human enhancer activity in 38,538 enhancers across 411 different contexts. In a machine-learning framework, the occurrence patterns of short sequence motifs accurately predicted broadly active human enhancers. However, DRMs alone were weakly predictive of broad enhancer activity in humans and showed different enrichment patterns than inDrosophila. In general, GC-rich sequence motifs were significantly associated with broad enhancer activity; consistent with this enrichment, broadly active human TFs recognize GC-rich motifs. Our results reveal the importance of specific sequence motifs in broadly active human enhancers, demonstrate the lack of evolutionary conservation of the role of DRMs, and provide a computational framework for investigating the logic of enhancer sequences.
Green and lean implementation: an assessment in the automotive industry
Authors: Duarte Susana , Cruz Machado V.
Published: February 2017

Purpose

The purpose of this research work is to propose an assessment framework to evaluate businesses in terms of the implementation of a green and lean organization’s supply chain.

Design/methodology/approach

A conceptual framework was developed for the assessment of green and lean implementation. The framework was designed using key criteria to identify green and lean initiatives. This led to the development of guidelines for each criterion, and the development of a scoring method. A multiple case study of five different organizations in the automotive industry was conducted to validate the conceptual framework.

Findings

The study reveals that high scores are derived from a good interaction between green and lean implementation in these companies. The results confirm that the initiatives considered in the conceptual framework were appropriate to represent the green and lean assessment framework.

Research limitations/implications

The case study was developed in five organizations. Validation of the model is not based on quantitative techniques. The sample size is too small. More study is need in different industry sectors.

Practical implications

The proposed model can be the basis for further research on green and lean concepts, contributing to the understanding of green and lean implementation. With this assessment method, managers can evaluate their business in relation to the implementation of green and lean supply chain initiatives.

Originality/value

To the author’s knowledge, this paper is the first to provide an assessment framework to evaluate an organization’s supply chain in terms of green and lean implementation.
Deviation of community savings groups from their apparent methodology
Authors: Maliti Emmanuel
Published: February 2017

Purpose

The purpose of this paper is to provide generalised views on ways in which field practice in Tanzania deviates from the village savings and lending associations (VSLA) methodology.

Design/methodology/approach

The research applied “participant observation method” involving actual participation in the weekly meetings of the surveyed savings groups.

Findings

Field practices deviate from the VSLA methodology. Deviations include the tendency for the savings groups to simplify financial intermediation by regressing from using loan guarantors, relying on external enforcement to recover debts from group members (rather than depending on within group enforcement mechanisms), use of social funds to recover loans, limited attendance in weekly group meetings and accumulation of debts towards share-out dates.

Research limitations/implications

Results from this study are relevant to Ilala district where VSLA groups were sampled from. Cautious reading is therefore necessary when attempting to generalise findings to other areas with different social, economic and institution settings.

Practical implications

VSLA model needs to consider a number of issues. They include devising means to accommodate field realities; from simplification of financial intermediation activities to the dependence of the savings groups on external enforcement.

Social implications

Social implications include a possible improved VSLA model based on the findings from this study, to further advance the performance of community-based savings groups.

Originality/value

By revealing the deviation of the VSLA methodology from the practice, the study adds value to the literature which is largely dominated by economic and poverty impact of savings groups.
Agricultural structure and farmers’ interconnections with rural communities
Authors: Besser T. , Jurt C. , Mann S.
Published: February 2017

Purpose

In the context of rural development, the question how farmers are interconnected with local rural communities is crucial, as farmers historically have played a key role in rural areas, always shaped by the cultural-systemic context in which they acted. The purpose of this paper is to explore this connection in North-East (NE) Germany and Switzerland, two countries whose agricultural systems can be seen as diametrically opposed to each other with respect to their structure.

Design/methodology/approach

The authors conducted a survey on NE German and Swiss farmers to assess the connectivity between farms and rural communities in terms of the farm managers’ perceptions of their social networks, social support, sense of belonging, and active involvement in organizations.

Findings

The results show commonalities and differences between both study regions. Smaller farms are characterized by strongly locally based networks and a higher sense of community belonging, whereas larger farms rather have networks with strong ties outside the local dimension. Moreover, farmers’ local origin and farm diversification are positively associated with strengthening the connection between farms and local communities. Off-farm work is a means for this connection only in NE Germany.

Originality/value

This paper contributes to the discussion about adverse effects of farming scale and corporate farming on community well-being by simultaneously delivering insights into two structurally different agricultural systems. At the same time the approach allows for a comparison between the systems.
A new method for CDP input parameter identification of the ABAQUS software guaranteeing uniqueness and precision
Authors: Labibzadeh Mojtaba , Zakeri Mojtaba , Adel Shoaib Abdol
Published: February 2017

Purpose

The purpose of this paper is to present a new method for determining the input parameters of the concrete damaged plasticity (CDP) model of ABAQUS standard software. The existing available methods in the literatures are case sensitive, i.e., they give different input parameters of CDP for a unique concrete class used in different finite element (FE) simulation of concrete structures. In this study, the authors attempt to introduce a new approach for the identification of the input parameters of the CDP model, which guarantees the uniqueness and precision of the model. In other words, by this method, the input parameters obtained for a specific concrete class with a unique characteristic strength can be used for FE simulation of the different concrete structures which were constructed by this concrete without the need to additional modifications raised from any new application.

Design/methodology/approach

For the input parameter identification of the CDP model, different standard tests of plain concrete are simulated by the ABAQUS standard software. These test simulations are performed for various set of input parameters. In the end, those set of input parameters which represents the best curve fitting with the experimental results is chosen as the optimum parameters.

Findings

By comparison of the FE simulation results obtained from the ABAQUS for two different concrete structures using the proposed input parameters for the CDP model with the experimental results, it was shown that the presented method for determining those parameters can guarantee the uniqueness and precision of the CDP model in simulation.

Originality/value

The method described for determining the input parameters of the CDP model of the ABAQUS standard software has not been previously presented.
The shockwave dispersion/attenuation potential of a protective structure made of a chemically reactive mixture
Authors: Grujicic Mica , Ramaswami S. , Snipes Jennifer
Published: February 2017

Purpose

In the recent work, a new blast-wave impact-mitigation concept involving the use of a protective structure consisting of bimolecular reactants (polyvinyl pyridine+cyclohexyl chloride), capable of undergoing a chemical reaction (to form polyvinyl pyridinium ionic salt) under shockwave loading conditions, was investigated using all-atom reactive equilibrium and non-equilibrium molecular-dynamics analyses. The purpose of this paper is to reveal the beneficial shockwave dispersion/attenuation effects offered by the chemical reaction, direct simulations of a fully supported single planar shockwave propagating through the reactive mixture were carried out, and the structure of the shock front examined as a function of the extent of the chemical reaction (i.e. as a function of the strength of the incident shockwave). The results obtained clearly revealed that chemical reactions give rise to considerable broadening of the shockwave front. In the present work, the effect of chemical reactions and the structure of the shockwaves are investigated at the continuum level.

Design/methodology/approach

Specifically, the problem of the (conserved) linear-momentum accompanying the interaction of an incident shockwave with the protective-structure/protected-structure material interface has been investigated, within the steady-wave/structured-shock computational framework, in order to demonstrate and quantify an increase in the time period over which the momentum is transferred and a reduction in the peak loading experienced by the protected structure, both brought about by the occurrence of the chemical reaction (within the protective structure).

Findings

The results obtained clearly revealed the beneficial shock-mitigation effects offered by a protective structure capable of undergoing a chemical reaction under shock-loading conditions.

Originality/value

To the authors’ knowledge, the present manuscript is the first report dealing with a continuum-level analysis of the blast-mitigation potential of chemical reactions.
Investigating agent-based inter-organizational systems and business network performance
Authors: Wasesa Meditya , Stam Andries , van Heck Eric
Published: February 2017

Purpose

From the theoretical perspectives of both multi-agent systems and smart business networks, empirical studies analyzing agent-based inter-organizational systems (ABIOS) in a real-life business setting are rare. The purpose of this paper is to investigate the impact of ABIOS on the performance of business networks.

Design/methodology/approach

This study presents a theoretical conceptual model portraying the influence of ABIOS on clients’ coordination structure and information architecture; and the impact of those structural alterations on business network performance in terms of the coordination, agility, and informational performances. To validate the model, a cross-case analysis was conducted in three logistics cases, namely, warehousing, freight forwarding, and intermodal transportation.

Findings

The application of ABIOS requires adjustments to the information architecture or the coordination structure, or both. Subsequently, those structural adjustments will stimulate improvements in the coordination, agility, and informational performances.

Research limitations/implications

The assessment of the clients’ performance improvement is done at the company level not at an aggregate network level. Moreover, the study only covers cases from the logistics sector.

Practical implications

This study explains the structural consequences of ABIOS applications. The adoption of an inter-organizational system is a strategic decision that requires support from multi-stakeholders. While the applications of ABIOS can offer performance improvement opportunities, adjustments must be made to the existing coordination structure or the information architecture, or both.

Originality/value

This study contributes to the smart business network literature and the ABIOS literature by presenting a validated conceptual model explaining the interplay among ABIOS, the coordination structure, informational structure, and business network performance, namely, the coordination, agility, and informational performances.
The impact of knowledge management on job performance in higher education
Authors: Masa’deh Ra’ed , Shannak Rifat , Maqableh Mahmoud , Tarhini Ali
Published: February 2017

Purpose

This is an empirical study of knowledge management performance (KMP) at a university and the purpose of this paper is to examine the relationship between knowledge management process (KMPR), KMP and job performance (JP).

Design/methodology/approach

The data were collected using a questionnaire, as the instrument for the primary data collection, with total collected back responses of 207 from university lecturers who have actually participated. Structural equation modeling technique was used to fully analyze the data in order to determine what level of the relationship between knowledge management (KM) and JP existed.

Findings

The main findings were related to confirming the two main hypotheses of the research that were related to testing if there were relationships between the KMPR (represented by seven surrogate measures, namely, knowledge identification, knowledge creation, knowledge collection, knowledge organizing, knowledge storage, knowledge dissemination and knowledge application) and KMP, as well as if the KMP was related to the JP.

Originality/value

This paper focuses on investigating the actual role of KM at a university, which is assumingly a knowledge factory. Contrary to the conventional wisdom that presumes the importance of KM and specially when there is no proper KM regiment in place, the paper reports the limited influence KM has on staff JP. It is one of the few studies that fills the gap in the literature concerned with the relationship between KM and JP and perhaps the first to provide insights about the KM intricacies at a Jordanian University.
Enabling internet banking adoption
Authors: Marakarkandy Bijith , Yajnik Nilay , Dasgupta Chandan
Published: February 2017

Purpose

The integration of relevant antecedents into TAM would lead to better understanding of the decision factors which act as enablers for the adoption of internet banking. The purpose of the paper is to determine the influence of the antecedents subjective norm, image, banks initiative, internet banking self-efficacy, internet usage efficacy, trust, perceived risk, trialability and government support on the existing constructs of the technology acceptance model (TAM) and to test measurement invariance and the moderating effect of the demographic variables on the relationship between the latent constructs used in this augmented TAM.

Design/methodology/approach

A survey questionnaire was administered on internet banking users and a total of 300 responses were collected. A two-step approach suggested by Hair et al. (2006) and Schumacker and Lomax (2004) was used in this study. The proposed model was assessed using the confirmatory factor analysis approach. The structural model was then tested in order to establish nomological validity. The data based on four demographic dimensions gender, age, income, education were divided into two groups for each of these demographic dimensions. The invariance test was first performed on the measurement model and then on the structural model. The measurement model and structural model were subjected to tests of equivalence of parameters across groups.

Findings

To a large extent the results of the study supports the proposed model and thereby contributes to understand the influence of subjective norm, image, banks initiative, internet banking self-efficacy, internet usage efficacy, trust, perceived risk and government support on internet banking adoption. The predictor variables in the augmented TAM were able to explain 29.9 per cent of the variance in the actual usage of internet banking as compared to the TAM which was able to explain only 26.5 per cent variance in the actual usage of internet banking. A significant difference in the relationship between the different constructs of the model was observed when the model was subjected to multi-group invariance testing.

Research limitations/implications

The study suffers from the same limitations as most other studies involving TAM. In this study self-reported measures about the usage were taken as the actual usage. The findings of the study can be of use to marketers for target-specific marketing by customizing the marketing campaign focussing on the factors that were found to be strong influencers leading to the usage of internet banking for each target audience.

Originality/value

The main challenge in this study was to develop the conceptual model for the internet banking adoption by extending the TAM and to get a robust theoretical support from the extant literature for the relevant factors along with their relationship to uncover new insights about factors responsible for the internet banking adoption. The augmented model had an improved predictive capability and explanatory utility.
Stanley Hollander’s T-shirt test: where marketing history meets psychogeography
Authors: Brown Stephen
Published: February 2017

Purpose

The aim of this overview is to reflect on the family resemblances between psychogeography and marketing history.

Design/methodology/approach

The paper is informally predicated on the perspectives and philosophies of literary theory in general and New Historicism in particular.

Findings

Using exemplar excerpts from salient published works, marketing’s hitherto overlooked psychogeographical traditions are contemplated and celebrated, the sterling contributions of Stanley C. Hollander above all.

Research limitations/implications

Like poets who don’t know it, marketing historians are unsung contributors to the psychogeographical corpus. There is much more that can be done, however, especially in relation to works of imaginative literature.

Originality/value

This paper aims to uncover past achievements not advance the future agenda.
The Griffiths Question Map: A Forensic Tool For Expert Witnesses’ Assessments of Witnesses and Victims’ Statements
Authors: Dodier Olivier , Denault Vincent
Published: February 2017

Expert witnesses are sometimes asked to assess the reliability of young witnesses and victims’ statements because of their high susceptibility to memory biases. This technical note aims to highlight the relevance of the Griffiths Question Map (GQM) as a professional forensic tool to improve expert witnesses’ assessments of young witnesses and victims’ testimonies. To do so, this innovative question type assessment grid was used to proceed to an in‐depth analysis of the interview of an alleged 13‐year‐old victim of a sexual assault and two rapes. Overall, the GQM stressed how the interview was mainly conducted in an inappropriate manner. The results are examined with regard to scientific knowledge on young witnesses and victims’ memory. Finally, it is argued that expert witnesses in inquisitorial systems might use the GQM while encountering difficulties to fulfill the legal standards for expert evidence in adversarial systems because of the lack of studies regarding its reliability.
Performance of the predator Amblyseius swirskii (Acari: Phytoseiidae) on greenhouse eggplants in the absence and presence of pine Pinus brutia (Pinales:Pinaceae) pollen
Authors: Kutuk Halil
Published: February 2017

In Turkey, the western thrips Frankliniella occidentalis (Pergande) is a key pest affecting eggplants grown in greenhouses for which an appropriate control strategy is under investigation. It was observed in a previous study that the release of the beneficial predatory mite Amblyseius swirskii (Athias‐Henriot) alone did not result in an effective control of thrips on eggplants. Since pollen is known to improve control efficiency of predators, this study was undertaken to investigate if provision of pollen to eggplants can greatly improve the efficiency of A. swirskii in controlling thrips. The experiments were carried out in both greenhouse and low tunnel. The provision of pollen led to a significant increase in the predator population density on the eggplants but did not result in an effective control of the thrips populations. In this paper, various factors are discussed that could have affected the efficiency of the predatory mite in controlling F. occidentalis on eggplants.
Salvage surgery for primary lung cancer after chemotherapy in octogenarians
Authors: Hino Haruaki , Nishimura Takashi , Usuki Chiemi , Sazuka Manami , Ito Takuya , Seki Atsuko , Nitadori Jun‐ichi , Yamada Hirokazu , Arai Tomio , Yamamoto Hiroshi , Nakajima Jun
Published: February 2017

An 81‐year‐old female patient was admitted to our institute because of abnormal X‐ray results. Chest computed tomography showed a 7.7 × 5.3 cm mass located in the left lower lobe and multiple swollen lymph nodes. 18F‐fluorodeoxyglucose‐positron emission tomography indicated high standard uptake values in the mass and swollen lymph nodes. The patient was diagnosed with stage cT3N2M0‐IIIA squamous cell carcinoma. Although the patient had multiple lymph node metastases and severe obstructive pulmonary function, four cycles of platinum doublet chemotherapy were initially performed and no side effect greater than grade 3 was experienced. As the lung cancer was downstaged to ycT2aN0M0‐IB and pulmonary function had improved, a bronchodilating preparation, an uneventful left lower lobectomy, and a lymphadenectomy were performed. The patient was discharged 39 days after surgery and exhibited good health for a year at pathological stage ypT1aN0M0‐IA (Ef2).
Patients with non‐substance‐related disorders report a similar profile of childhood trauma experiences compared to heroin‐dependent patients
Authors: Schwaninger Philipp V. , Mueller Sandra E. , Dittmann Rebecca , Poespodihardjo Renanto , Vogel Marc , Wiesbeck Gerhard A. , Walter Marc , Petitjean Sylvie A.
Published: February 2017

Background and Objectives

Exposure to traumatic events is common among patients with substance use disorders (SUD). In patients with non‐substance‐related disorders, especially with gambling disorders (GD) and internet addiction (IA), traumatic childhood experiences have not been investigated extensively. The objective of this study was to compare trauma histories in patients with GD and IA to patients with heroin dependence.

Methods

Cross‐sectional surveys including the childhood trauma questionnaire (CTQ) and clinical data among 107 participants; 59 patients with non‐substance‐related disorders (GD [n = 39]; IA [n = 20]) were compared to 28 patients prescribed injectable heroin for opioid dependence in heroin‐assisted treatment (HAT) and to a healthy control group (HC) (n = 20).

Results

The findings revealed a high prevalence of trauma exposure in all three clinical groups, with 74.4% of patients with GD, 80.0% of patients with IA, and 93.0% of patients in HAT compared to 40% in HC. All three groups (GD, IA, HAT) reported significantly higher levels of “emotional neglect” compared to HC.

Conclusions and Scientific Significance

The results provide clinically relevant information suggesting that the burden of childhood traumatic experiences may be as common in patients with GD and IA as in patients with heroin dependence. These findings could pose an important starting‐point for treatment. (Am J Addict 2017;26:215–220)
Upregulated expression of La ribonucleoprotein domain family member 6 and collagen type I gene following water‐filtered broad‐spectrum near‐infrared irradiation in a 3‐dimensional human epidermal tissue culture model as revealed by microarray analysis
Authors: Tanaka Yohei , Nakayama Jun
Published: February 2017

Background/Objectives

Water‐filtered broad‐spectrum near‐infrared irradiation can induce various biological effects, as our previous clinical, histological, and biochemical investigations have shown. However, few studies that examined the changes thus induced in gene expression. The aim was to investigate the changes in gene expression in a 3‐dimensional reconstructed epidermal tissue culture exposed to water‐filtered broad‐spectrum near‐infrared irradiation.

Methods

DNA microarray and quantitative real‐time polymerase chain reaction (PCR) analysis was used to assess gene expression levels in a 3‐dimensional reconstructed epidermal model composed of normal human epidermal cells exposed to water‐filtered broad‐spectrum near‐infrared irradiation. The water filter allowed 1000–1800 nm wavelengths and excluded 1400–1500 nm wavelengths, and cells were exposed to 5 or 10 rounds of near‐infrared irradiation at 10 J/cm2.

Results

A DNA microarray with over 50 000 different probes showed 18 genes that were upregulated or downregulated by at least twofold after irradiation. Quantitative real‐time PCR revealed that, relative to control cells, the gene encoding La ribonucleoprotein domain family member 6 (LARP6), which regulates collagen expression, was significantly and dose‐dependently upregulated (P < 0.05) by water‐filtered broad‐spectrum near‐infrared exposure. Gene encoding transcripts of collagen type I were significantly upregulated compared with controls (P < 0.05).

Conclusions

This study demonstrates the ability of water‐filtered broad‐spectrum near‐infrared irradiation to stimulate the production of type I collagen.
Low‐dose prednisone and immunoglobulin G treatment for woman at risk for neonatal alloimmune thrombocytopenia and T helper 1 immunity
Authors: Skariah Annie , Sung Nayoung , Salazar Garcia Maria D. , Wu Li , Tikoo Anjali , Gilman‐Sachs Alice , Kwak‐Kim Joanne
Published: February 2017

Problem

Fetal and neonatal alloimmune thrombocytopenia is an alloimmune disorder resulting from platelet opsonization by maternal antibodies that destroy fetal platelets. As there is no antenatal screening or immunization to prevent sensitization, selection of high‐risk population or the prevention of antenatal sensitization is significantly limited.

Method of study

(i) A case report of ante‐ and postnatal management of a woman with paternal homozygosity for human platelet antigen‐1(HPA) incompatibility. (ii) A retrospective case‐control study of 11 confirmed FNAIT patients, 8 possible‐FNAIT women, and 10 women with confirmed ITP.

Result

Antenatal screening, prevention of maternal sensitization by serial monitoring and immunosuppression with prednisone and intravenous immunoglobulin G (IVIG) infusion resulted in two successful pregnancies without sensitization.

Conclusion

Screening for couples at risk and prednisone and/or IVIG treatment is an option for women with paternal homozygosity for offending HPA antigen to prevent antenatal sensitization. HPA incompatibility is associated with increased Th1 immunity and NK cell cytotoxicity.
Vagal nerve stimulation reduces infarct size via a mechanism involving the alpha‐7 nicotinic acetylcholine receptor and downregulation of cardiac and vascular arginase
Authors: Kiss A. , Tratsiakovich Y. , Mahdi A. , Yang J. , Gonon A. T. , Podesser B. K. , Pernow J.
Published: February 2017

Aims

Vagal nerve stimulation (VNS) protects from myocardial and vascular injury following myocardial ischaemia and reperfusion (IR) via a mechanism involving activation of alpha‐7 nicotinic acetylcholine receptor (α7 nAChR) and reduced inflammation. Arginase is involved in development of myocardial IR injury driven by inflammatory mediators. The aim of the study was to clarify whether VNS downregulates myocardial and vascular arginase via a mechanism involving activation of α7 nAChR following myocardial IR.

Methods

Anaesthetized rats were randomized to (i) sham‐operated, (ii) control IR (30‐min ischaemia and 2‐h reperfusion, (iii) VNS throughout IR, (iv) the arginase inhibitor nor‐NOHA+IR, (v) nor‐NOHA+VNS+IR, (vi) selective α7 nAChR blockade by methyllycaconitine (MLA) followed by VNS throughout IR and (vii) MLA+IR.

Results

Infarct size was reduced by VNS compared to control IR (41 ± 3% vs. 67 ± 2% of the myocardium at risk, P < 0.001). Myocardial IR increased myocardial and aortic arginase activity 1.7‐ and 3.1‐fold respectively (P < 0.05). VNS attenuated the increase in arginase activity compared to control IR both in the myocardium and aorta (P < 0.05). MLA partially abolished the cardioprotective effect of VNS and completely abrogated the effect of VNS on arginase activity. Arginase inhibition combined with VNS did not further reduce infarct size.

Conclusion

Vagal nerve stimulation reduced infarct size and reversed the upregulation of arginase induced by IR both in the myocardium and aorta via a mechanism depending on α7 nAChR activation. The data suggest that the cardioprotective effect of VNS is mediated via reduction in arginase activity.
Systematic review with meta‐analysis: the efficacy and safety of CT‐P13, a biosimilar of anti‐tumour necrosis factor‐α agent (infliximab), in inflammatory bowel diseases
Authors: Komaki Y. , Yamada A. , Komaki F. , Micic D. , Ido A. , Sakuraba A.
Published: February 2017

Background

Biosimilars of anti‐tumour necrosis factor (TNF)‐α agents have now become clinically available for the treatment of inflammatory bowel diseases (IBD).

Aim

To perform a systematic review and meta‐analysis to evaluate the efficacy and safety of biosimilars of anti‐TNF‐α agents in patients with IBD.

Methods

Electronic databases were searched. The outcomes were the pooled rates of clinical response or remission, sustained clinical response or remission, and adverse events in patients with IBD induced with or switched to biosimilars of anti‐TNF‐α agents.

Results

Eleven observational studies reporting outcomes in 829 patients treated with biosimilar of infliximab (CT‐P13) were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8–14 weeks were 0.79 (95% confidence interval (CI) = 0.65–0.88) and 0.74 (95% CI = 0.65–0.82), respectively, and at 24–30 weeks were 0.77 (95% CI = 0.63–0.86) and 0.77 (95% CI = 0.67–0.85) respectively. Adverse events were rare (CD, 0.08 (95% CI = 0.02–0.26); UC, 0.08 (95% CI = 0.03–0.17)). The pooled rates of sustained clinical response among CD and UC after switching from infliximab to CT‐P13 at 30–32 weeks were 0.85 (95% CI = 0.71–0.93) and 0.96 (95% CI = 0.58–1.00), respectively, and at 48–63 weeks were 0.75 (95% CI = 0.44–0.92) and 0.83 (95% CI = 0.19–0.99) respectively. Adverse events were rare (CD, 0.10, 95% CI = 0.02–0.31; UC, 0.22, 95% CI = 0.04–0.63).

Conclusions

CT‐P13 was associated with excellent clinical efficacy and safety profile, supporting its use in the treatment of IBD.
Intra‐patient variability in adalimumab drug levels within and between cycles in Crohn's disease
Authors: Ward M. G. , Thwaites P. A. , Beswick L. , Hogg J. , Rosella G. , Van Langenberg D. , Reynolds J. , Gibson P. R. , Sparrow M. P.
Published: February 2017

Background

Whether therapeutic drug monitoring for adalimumab needs to be performed at trough has not been defined.

Aim

To determine intra‐patient adalimumab drug‐level variation and to identify modulating patient and disease factors.

Methods

In this prospective observational study, adult patients with Crohn's disease established on maintenance adalimumab had drug levels measured repeatedly according to pre‐defined schedules (visit 1: day 4–6, visit 2: day 7–9, trough: day 13–14) across two consecutive fortnightly cycles. Disease activity was assessed using Harvey–Bradshaw Index, C‐reactive protein and faecal calprotectin. For this analysis, trough levels ≥4.9 μg/mL were considered therapeutic.

Results

Nineteen patients underwent 111 evaluations. Mean intra‐patient drug levels from paired visits between cycles did not differ (visit1 cycle1: 4.81, cycle2: 5.21 μg/mL, P = 0.24, visit2 cycle1: 4.86, cycle2: 4.82, P = 0.91 and trough cycle1: 3.95, cycle2: 3.95, P = 0.99), irrespective of disease activity. Drug levels were stable over the first 9 days (visit 1–2), but declined to trough by a mean 1.06 and 0.89 μg/mL between visit 1 or 2, respectively (P < 0.001). Models using nontemporal factors (smoking, syringe delivery device) and levels at earlier visits accounted for 66–80% of the variance in trough levels. On receiver‐operating curve analysis, thresholds identified in the first 9 days that predicted a therapeutic trough level were similar to the trough threshold itself, with high sensitivity but modest specificity.

Conclusion

While therapeutic drug monitoring should be performed at trough, a drug level ≥4.9 μg/mL obtained during the first 9 days predicts a therapeutic trough drug level with reasonable confidence.
The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis
Authors: Smolinska A. , Bodelier A. G. L. , Dallinga J. W. , Masclee A. A. M. , Jonkers D. M. , van Schooten F.‐J. , Pierik M. J.
Published: February 2017

Background

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non‐invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non‐UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease.

Aim

To investigate whether VOCs are able to differentiate between active UC, UC in remission and non‐UC colitis.

Methods

UC patients participated in a 1‐year study. Clinical activity index, blood, faecal and breath samples were collected at each out‐patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C‐reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross‐sectional analysis. Non‐UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time‐of‐flight mass spectrometry and kernel‐based method to identify discriminating VOCs.

Results

In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non‐UC‐colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non‐UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis.

Conclusions

Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non‐UC colitis patients. VOCs have demonstrated potential as new non‐invasive biomarker to monitor inflammation in UC.
Long‐term use of oral nucleos(t)ide analogues for chronic hepatitis B does not increase cancer risk – a cohort study of 44 494 subjects
Authors: Wong G. L.‐H. , Tse Y.‐K. , Yip T. C.‐F. , Chan H. L.‐Y. , Tsoi K. K.‐F. , Wong V. W.‐S.
Published: February 2017

Background

Patients with chronic hepatitis B (CHB) need long‐term antiviral treatment with nucleos(t)ide analogues (NA). Animal studies suggest that some NA may increase cancer risk, but human data are lacking.

Aim

To investigate cancer risks in patients with or without NA treatment.

Methods

We conducted a territory‐wide cohort study using the database from Hospital Authority in Hong Kong. The diagnosis of CHB and various malignancies was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis codes between 2000 and 2012. Patients exposed to any of the oral NA for CHB were included. The primary outcome was incident cancers. A 3‐year landmark analysis, with follow‐up up to 7 years, was used to evaluate the relative risk of cancers in treated and untreated patients.

Results

A total of 44 494 patients (39 712 untreated and 4782 treated) were included in the analysis. During 194 890 patient‐years of follow‐up, hepatocellular carcinoma developed in 402 (1.0%) untreated patients and 179 (3.7%) treated patients, while other cancers developed in 528 (1.3%) and 128 (2.7%) patients respectively. After propensity score weighting, treated patients had similar risks of all malignancies [weighted hazard ratio (wHR): 1.01, 95% CI: 0.82–1.25, P = 0.899], lung/pleural cancers (wHR: 0.82, 95% CI: 0.52–1.31, P = 0.409) and urinary/renal malignancies (wHR: 1.04, 95% CI: 0.38–2.81, P = 0.944) when compared with untreated patients.

Conclusions

Oral nucleos(t)ide analogue treatment does not appear to increase cancer risk in patients with chronic hepatitis B. Given the beneficial effect on liver outcomes, our data support the current practice of long‐term anti‐viral therapy.
Hypovitaminosis A in extensively grazed beef cattle
Authors: Parker EM , Gardiner CP , Kessell AE , Parker AJ
Published: February 2017

Case report

Vitamin A deficiency was diagnosed in a herd of 97 19‐month‐old Braford heifers in the Mitchell Grass Downs (Astrebla spp.) bioregion of Hughenden in north‐western Queensland during November 2015. Two heifers died after a 48‐h history of sternal recumbency and of the 19 that had neurological signs, 7 were blind. Histological changes in the optic nerves of the two necropsied cattle were consistent with vitamin A deficiency. This diagnosis was supported by vitamin A concentrations in fresh liver samples of 5 and 6 mg/kg wet tissue (reference range, 100–175 mg/kg) despite treatment of the cattle with twice the recommended dose of parenteral vitamin A 3 weeks prior to sampling. Rainfall on the property during the 2 years before the outbreak was less than the annual rainfall average of 464 mm, with a total of 281 mm in 2014 and 117 mm from January to November in 2015, most of this falling in January.

Conclusion

Plant assays for both β‐carotene and crude protein concentrations in dry matter (DM) were less than the recommended dietary requirements for beef cattle (0.30 mg/kg DM and 56 g/kg, respectively).
Neospora caninum in beef herds in New South Wales, Australia. 1: seroprevalence study
Authors: Moloney BJ , Kirkland PD , Heuer C
Published: February 2017

Objective

To determine the seroprevalence of Neospora caninum antibodies in beef breeding herds across New South Wales (NSW) and to determine if there are any differences associated with geographic location and other herd‐level factors.

Methods

Cross‐sectional survey of beef breeding cows (n = 3298) from 63 properties (approximately 55 cows per herd) sampled randomly from six regions in NSW using a multistage survey design. Samples were tested by ELISA for N. caninum. Seroprevalence was determined at animal and herd levels, using an analysis approach to account for stratification, sample weighting and within‐herd clustering.

Results

Animal‐level seroprevalence ranged from 1.8% to 11.3% across regions and the overall animal seroprevalence for NSW was 5.9%. The mean within‐herd seroprevalence was 5.2%. The herd seroprevalence ranged from 50% to 92%, with an overall point estimate for NSW of 63.8% (using ≥ 1 animal positive = herd positive). The within‐herd seroprevalence ranged from 1.6% to 32.7% Prevalence and associated confidence limits were adjusted for the design of the survey.

Conclusions

Overall, about two‐thirds of all herds in NSW showed evidence of infection, but the seroprevalence of N. caninum in individual beef cattle in NSW was low to moderate (1.8–11.3%). Significant differences occurred between regions. The risk for herds being positive for N. caninum was associated with geographic factors, particularly in the Mid‐North Coast Region.
Increased hippocampal, thalamus and amygdala volume in long‐term lithium‐treated bipolar I disorder patients compared with unmedicated patients and healthy subjects
Authors: López‐Jaramillo Carlos , Vargas Cristian , Díaz‐Zuluaga Ana M. , Palacio Juan David , Castrillón Gabriel , Bearden Carrie , Vieta Eduard
Published: February 2017

Objective

Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD‐I) suggest that lithium is associated with increased volumes of cortico‐limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long‐term lithium‐treated BD‐I patients, unmedicated BD‐I patients, and healthy controls.

Methods

This was a cross‐sectional study with 32 euthymic BD‐I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain.

Results

Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long‐term lithium‐treated BD‐I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas.

Conclusions

The structural differences found among the three groups, and specifically those between long‐term lithium‐treated and unmedicated BD‐I patients, indicate increased limbic structure volumes in lithium‐treated patients.
Is Consent Based on Trust Morally Inferior to Consent Based on Information?
Authors: Kongsholm Nana Cecilie Halmsted , Kappel Klemens
Published: February 2017

Informed consent is considered by many to be a moral imperative in medical research. However, it is increasingly acknowledged that in many actual instances of consent to participation in medical research, participants do not employ the provided information in their decision to consent, but rather consent based on the trust they hold in the researcher or research enterprise. In this article we explore whether trust‐based consent is morally inferior to information‐based consent. We analyse the moral values essential to valid consent – autonomy, voluntariness, non‐manipulation, and non‐exploitation – and assess whether these values are less protected and promoted by consent based on trust than they are by consent based on information. We find that this is not the case, and thus conclude that trust‐based consent if not morally inferior to information‐based consent.
Research on face recognition: The Aberdeen influence
Authors: Davies Graham M. , Young Andrew W.
Published: February 2017

The review of ‘Recognizing faces’ by Hadyn Ellis, published in the British Journal of Psychology in 1975, marked the genesis of a distinct field of research. This seminal review sprang from a broader programme of research on face recognition conducted at the University of Aberdeen, whose influence continues to be felt in what has become an internationally important research area. We discuss the background to the Aberdeen research, summarize some of its achievements, and offer reasons why it proved so successful. These reasons include the synergy between theory and practice‐based studies, the value of combining different perspectives and sources of evidence, sound techniques that led to easily reproducible findings, and the emphasis on testing even the most ‘common sense’ assumptions.
Stimulation of Na+‐K+‐pump currents by epithelial nicotinic receptors in rat colon
Authors: Bader Sandra , Lottig Lena , Diener Martin
Published: February 2017

Background and Purpose

Acetylcholine‐induced epithelial Cl− secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data have shown expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl− secretion by nicotine, in the presence of the neurotoxin, tetrodotoxin. Here, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport.

Experimental Approach

Ussing chamber experiments were performed, using rat distal colon with intact epithelia. Epithelia were basolaterally depolarized to measure currents across the apical membrane. Apically permeabilized tissue was also used to measure currents across the basolateral membrane in the presence of tetrodotoxin.

Key Results

Nicotine had no effect on currents through Cl− channels in the apical membrane or on currents through K+ channels in the apical or the basolateral membrane. Instead, nicotine stimulated the Na+‐K+‐pump as indicated by Na+‐dependency and sensitivity of the nicotine‐induced current across the basolateral membrane to cardiac steroids. Effects of nicotine were inhibited by nicotinic receptor antagonists such as hexamethonium and mimicked by dimethyl‐4‐phenylpiperazinium, a chemically different nicotinic agonist. Simultaneous stimulation of epithelial muscarinic and nicotinic receptors led to a strong potentiation of transepithelial Cl− secretion.

Conclusions and Implications

These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na+‐K+‐ATPase.