bluuebunny/crossref_metadata_2025 huggingface dataset:
A taxonomy of factors affecting attitudes towards educational technologies for use with technology acceptance models
Authors: Kemp Andrew , Palmer Edward , Strelan Peter
Published: June 2019

The aim of this theoretical review was to identify the important factors shown to affect attitudes towards use of educational technologies by students or educators in higher education institutions and organise them into broad, intermediate and narrow groupings. This was done to assist the construction of more objective measurement instruments used in the evaluation of educational technologies. A qualitative review of the influential factors that affect user attitudes, intentions and motivations to use educational technologies was conducted, first by interrogating the fundamental behavioural theories underpinning technology acceptance models, and then by exploring the findings of later and contemporary empirical research conducted in the educational context. Identified factors were grouped to produce an ordered taxonomy of measurement constructs. This taxonomy provides each construct’s lineage back through tertiary, secondary and primary taxonomic groups and provides a greater scope of measurement than commonly used models. Seven primary and twenty two secondary and tertiary taxonomic groups were defined, which collectively comprise sixty one measurement constructs. The taxonomy is designed to reduce measurement bias within studies and also acts as a basis for consistent and objective benchmarking within and across institutions.

Practitioner Notes

What is already known about this topic

Technology acceptance models are derived from a number of foundational behavioural and motivational theories.

The TAM and UTAUT are validated models that appraise attitude and/or behavioural intent to use an educational technology, which nonetheless do not cover the entire scope of what has been shown to be important in various studies.

There is little consistency from study to study of measurement constructs used in technology acceptance models.

What this paper adds

Collection and organisation of the salient measurement constructs into a flexible taxonomy.

Establishment of a consistent measurement scope that is specifically suited to educational technology research.

Establishment of construct lineage that clearly shows similarities and differences between the various constructs.

Implications for practice and/or policy

The taxonomy supports robust instrument construction to improve both convergent and discriminant validity of measurement models.

The taxonomy provides a recommended scope for higher education institutions to measure factors affecting use of various educational technologies.

Consistent use of the taxonomy will provide an objective standard that can be used to compare across institutions or within institutions over time, which assist with benchmarking and management decisions.

The taxonomy can be used as a framework for meta‐analyses or to collate ‘prior’ data to use in Bayesian‐type technology evaluation.
Teacher interventions in students’ collaborative work in a technology‐rich educational makerspace
Authors: Kajamaa Anu , Kumpulainen Kristiina , Olkinuora Helmi‐Riikka
Published: June 2019

This study reports on an investigation of teacher interventions in students’ collaborative work in an educational makerspace. We draw on a qualitative analysis of video data on teacher–student interaction derived from 94 students (aged 9–12) and their teachers in a Finnish school. The results show that the teacher interventions were both student‐ and teacher‐initiated. Three leading teacher intervention strategies were identified, namely authoritative, orchestrating and unleashing which emerged in teacher–student interactions dealing with conceptual, procedural, technological, behavioural and motivational issues. The study demonstrates the demands makerspaces pose for teacher–student interaction, and how moving from authoritative to collaborative interaction requires collective efforts and cultural change.
Characteristic dynamics of height and weight in preschool boys with constitutional delay of growth and puberty or hypogonadotropic hypogonadism
Authors: Reinehr Thomas , Hoffmann Elisa , Rothermel Juliane , Lehrian Theresa Johanna , Binder Gerhard
Published: June 2019

Objective

Constitutional delay of growth and puberty (CDGP) is a frequent variant of the normal leading to short stature and/or pubertal delay. To distinguish CDGP from hypogonadotropic hypogonadism (HH), we evaluated height, growth and weight pattern of CDGP and HH in the first 5 years of life.

Design and patients

We studied retrospectively height and weight in the first 5 years (y) of life in 54 boys with CDGP and 8 boys with HH.

Results

In boys with CDGP, height‐SDS decreased (change −0.94 (interquartile range [IQR] −1.69 to −0.05); P < 0.001) between birth and 2 years. BMI‐SDS decreased (change −0.38 (IQR −1.21‐0.16); P < 0.001) in the same time period. There were no significant changes in height‐SDS or BMI‐SDS between 2 years and 5 years, while height‐SDS (change + 1.49 (IQR 1.02‐1.95); P < 0.001) and BMI‐SDS (change + 0.91 (IQR 0.12‐1.69); P < 0.001) increased between pubertal and adult age. In boys with HH, height‐SDS and BMI‐SDS did not change significantly in the first 5 years of life. Height‐SDS decreased (change −1.39 (IQR −1.96 to −0.67); P = 0.018) significantly between 5 years of life and puberty, while there were no significant changes in BMI‐SDS in this time period. At pubertal age, BMI‐SDS was significantly (P = 0.001) higher in boys with HH compared with boys with CDGP.

Conclusion

Height deflection and weight deflection in CDGP occur already during the first two years of life in contrast to HH. This different pattern of growth and weight might be helpful to distinguish CDGP from HH.
Discoid resection for colorectal endometriosis: results from a prospective cohort from two French tertiary referral centres
Authors: Abo C. , Bendifallah S. , Jayot A. , Nyangoh Timoh K. , Tuech J.‐J. , Roman H. , Daraï E.
Published: June 2019

Aim

Using a prospective database of discoid resection performed in two tertiary referral centres, the aim of this study is to assess the feasibility, short‐term complication rates and clinical outcomes, including voiding dysfunction, of the procedure.

Method

A retrospective analysis of a prospective cohort database was conducted from February 2010 to October 2017 in two tertiary referral centres. One hundred and forty‐eight consecutive patients scheduled for colorectal endometriosis by discoid resection were enrolled. The median follow‐up was 21 months. All the women underwent complete preoperative assessment (MRI, transvaginal ultrasonography and rectal echo‐endoscopy) before the removal of colorectal endometriosis. Postoperative complications were classified according to the Clavien–Dindo classification system as minor (grades I and II) or major (grades IIIA, IIIB and IV). Cases of voiding dysfunction were also noted.

Results

The procedure was abandoned in seven patients. In 91 (64.5%) of the remaining 141 patients, the diameter of discoid resection removed was ≥ 30 mm. Surgery was performed by laparoscopy in 137/141 cases (92.7%). Grade I–III complications were observed in 37 patients (26.2%) with 11 grade IIIb (7.8%). Postoperative voiding dysfunction occurred in 16 patients (11.3%), 11 of whom required self‐catheterization for < 1 month. In a multivariate analysis including age, body mass index, lesion size and history of previous surgery for endometriosis, a history of previous surgery was independently correlated to complication outcome (P = 0.043).

Conclusions

This analysis suggests that discoid resection is associated with good short‐term results for women with colorectal endometriosis in a tertiary referral centre as it is associated with a low rate of postoperative complications.
Spindle epithelial tumour with thymus‐like elements presenting with lymph node metastasis: An illustrative case report with review of literature
Authors: Nambirajan Aruna , Singh Varsha , Irugu David Victor Kumar , Agarwal Shipra , Jain Deepali
Published: June 2019

Spindle epithelial tumor with thymus‐like elements is a quite rare and enigmatic tumor of uncertain histogenesis occurring within the thyroid. The authors present an illustrative case in a young female highlighting the cytomorphology, immunohistochemistry and molecular features, and discuss the diagnostic difficulties and therapeutic uncertainties encountered.
Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer
Authors: Pak Min Gyoung , Roh Mee Sook
Published: June 2019

Objective

Programmed cell death ligand‐1 (PD‐L1) has emerged as a predictive biomarker in lung cancer. PD‐L1 immunohistochemistry (IHC) assay predicts the response to immunotherapy, but cytology specimens are often the only samples available in a considerable proportion of advanced lung cancer patients. We delineate practical feasibility and efficacy of cytology cell‐block (CB) specimens for PD‐L1 expression and concordance between cytology CBs and surgical resection specimens.

Methods

In total, 58 eligible patients with primary lung cancer who received computed tomography‐guided percutaneous needle aspiration and surgery were included. PD‐L1 IHC (clone SP263) was performed on CBs prepared from residual liquid‐based cytology material and matched surgical resection specimens. PD‐L1 positive tumour cell proportion was categorised in four score groups: (a) <1%; (b) ≤1% to <10%; (c) ≤10% to <50%, (d) ≥50%.

Results

Comparison of PD‐L1 expression in cytology CBs and matched surgical resection specimens showed a high concordance (κ value 0.65). According to the therapeutic guideline of immunotherapeutic agents, a positive percent agreement was 94.34%, and a negative percent agreement was 100% at a cut‐off value for positivity of 1% PD‐L1 expression. There was a significant difference observed with regard to rates of PD‐L1 positivity when comparing smoking history (P = 0.02), age (P = 0.04) and pathological TNM stage (P = 0.04).

Conclusions

The results show that cytology CBs evaluated for PD‐L1 IHC assay have high concordance with matched surgical resection specimens and can be used for assessing PD‐L1 expression. Also, we propose that CBs are suitable materials for evaluating PD‐L1 expression while simultaneously performing both diagnostic and molecular tests.
Harmless? A hierarchical analysis of poppers use correlates among young gay and bisexual men
Authors: Demant Daniel , Oviedo‐Trespalacios Oscar
Published: June 2019

Introduction and Aims

Poppers (alkyl nitrites) are recreational substances commonly used during sexual activity. The current legal status of poppers is complex and wide‐ranging bans are increasingly under discussion. Research has identified disproportionate levels of poppers use in sexual minority men. While research on poppers use among sexual minority men exists, little is known about poppers use patterns and correlations with psychosocial and other factors among gay and bisexual young men.

Design and Methods

A cross‐sectional survey was conducted with 836 Australian gay and bisexual young men aged 18 to 35 years. Descriptive statistics and hierarchical segmentation analyses were conducted to identify poppers use patterns, and correlates of recent poppers use (past 3 months) with personal characteristics, use of other substances, as well as mental and psychosocial health including minority stress, LGBT‐community connectedness and participation.

Results

High levels of lifetime (38%, n = 315) and recent (24%, n = 204) poppers use were reported. However, few participants reported dependency symptoms, risky consumption or problems arising from using poppers. The final model included three variables (visiting sex‐on‐premises venues, licensed LGBT venues, and using other substances) and predicted 85% (n = 174) of recent poppers use. No correlations with other concepts or characteristics could be identified.

Conclusion

This analysis further supports the hypothesis that poppers may be substances with a comparably low‐risk profile. A regulation of poppers with a harm reduction approach may present a valuable public health intervention.
Successful endoscopic mucosal resection with over‐the‐scope clip for gastric cancer of fundic gland type apparently inappropriate for endoscopic submucosal dissection
Authors: Tashima Tomoaki , Nonaka Kouichi , Ryozawa Shomei
Published: June 2019

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(Technically) Difficult colonoscope insertion – Tips and tricks
Authors: Rodrigues‐Pinto Eduardo , Ferreira‐Silva Joel , Macedo Guilherme , Rex Douglas K.
Published: June 2019

Cecal intubation is a critical aspect of effective, complete colonoscopy. Difficult colonoscopy is most often considered as one in which it is challenging or impossible to reach the cecum. It may be a common occurrence due to patient and/or endoscopist factors. Incomplete colonoscopies should be avoided, since patients in this context present an important prevalence of lesions that escape examination. The approach to successful cecal intubation should depend on characterization of the problem as redundant colon or difficult sigmoid colon. Most patients with a prior incomplete colonoscopy can be colonoscoped successfully, if careful attention is paid to technique, using a variety of scopes, colonoscopy methods and additional equipment. Sufficient time should be allotted to make the attempt.
AFTER THE TOURNAMENT: OUTCOMES AND EFFORT PROVISION
Authors: McGee Andrew , McGee Peter
Published: June 2019

Outcomes of workplace competitions may themselves influence subsequent behavior—particularly if employees feel wronged. In a laboratory experiment, we find that—consistent with inequity aversion—tournament losers supply less postcompetition effort than winners when doing so reduces their tournament opponent's earnings. Consistent with procedural fairness concerns, subjects who lose arbitrarily decided tournaments that disregard tournament effort choices supply even less post‐tournament effort than other losers. While losers' effort reductions consistent with inequity aversion persist, effort reductions following arbitrarily decided tournaments fade over time. Finally, we show that effort reductions related to inequity aversion could potentially be mitigated through workplace rotations. (JEL C90, J30, D03)
Fish assemblage convergence along stream environmental gradients: an intercontinental analysis
Authors: Bower Luke M. , Winemiller Kirk O.
Published: June 2019

Species that pass through similar environmental filters, regardless of geographic proximity or evolutionary history, are expected to share many traits, resulting in similar assemblage trait distributions. Convergence of assemblage trait distributions among different biotic regions would indicate that consistent ecological processes produce repeated patterns of adaptive evolution. This study analyzes trait–environment relationships across multiple stream fish assemblages representing evolutionarily divergent faunas. We hypothesized that trait–environment patterns converge across regional faunas in response to a common set of environmental filters acting on functional traits. One hundred and ninety‐seven species and forty streams were sampled from five regions: Belize, Benin, Brazil, Cambodia and USA. By examining trait–environment plots, multiple congruent trait–environment patterns were found across all regions, indicative of a consistent set of environmental filters acting on local community assembly. The consistency of these patterns strongly suggests that water velocity and habitat structural complexity function as universal environmental filters, producing similar assemblage trait distributions in streams across all regions. Bivariate relationships were not universal, and only one of the associations between a single functional trait and single environmental variable was statistically significant across all five regions. Strong phylogenetic signal was found in traits and habitat use, which implies that niche conservatism also influenced assemblage trait distributions. Overall, results support the idea that habitat templates structure trait distributions of stream fish assemblages and do so in a consistent manner.
Evolution of nodal and nodal‐related genes and the putative composition of the heterodimers that trigger the nodal pathway in vertebrates
Authors: Opazo Juan C. , Kuraku Shigehiro , Zavala Kattina , Toloza‐Villalobos Jessica , Hoffmann Federico G.
Published: June 2019

Nodal is a signaling molecule that belongs to the transforming growth factor‐β superfamily that plays key roles during the early stages of development of animals. In vertebrates Nodal forms an heterodimer with a GDF1/3 protein to activate the Nodal pathway. Vertebrates have a paralog of nodal in their genomes labeled Nodal‐related, but the evolutionary history of these genes is a matter of debate, mainly because of the presence of a variable numbers of genes in the vertebrate genomes sequenced so far. Thus, the goal of this study was to investigate the evolutionary history of the Nodal and Nodal‐related genes with an emphasis in tracking changes in the number of genes among vertebrates. Our results show the presence of two gene lineages (Nodal and Nodal‐related) that can be traced back to the ancestor of jawed vertebrates. These lineages have undergone processes of differential retention and lineage‐specific expansions. Our results imply that Nodal and Nodal‐related duplicated at the latest in the ancestor of gnathostomes, and they still retain a significant level of functional redundancy. By comparing the evolution of the Nodal/Nodal‐related with GDF1/3 gene family, it is possible to infer that there are several types of heterodimers that can trigger the Nodal pathway among vertebrates.
Retracted: Bevacizumab synergises with the BCL 2 inhibitor venetoclax to effectively treat B‐cell non‐Hodgkin's lymphoma
Authors: Wang Li , Peng Shaoyong , Sun Weipeng , Liu Xiaoxia
Published: June 2019

Objectives

Our present study has shown a potential role for VEGF‐A‐mediated autocrine signalling to promote survival and proliferation of SU‐DHL‐6 cells, but the cells could not undergo apoptosis but rather decrease proliferation after bevacizumab treatment. Therefore, we would like to further study the antitumour efficacy of venetoclax (BCL2 inhibitor) in combination with bevacizumab in B‐cell NHL.

Methods

The human cytokine antibody array, RT‐qPCR, Western blot, ELISA, apoptosis assay and xenografted mouse model et al were used.

Results

We described a unique phenomenon that SU‐DHL‐6 cells showed cell density‐dependent survival and growth. Then, we suggested the expression of VEGF‐A was positively correlated with the cell density using a human cytokine antibody array and indicated an important role of VEGF‐A in the survival and proliferation of SU‐DHL‐6 cells. Additionally, xenografted SU‐DHL‐6 cells formed tumours in mice that grew in response to VEGF stimulation. GEO data set also suggested that high VEGF‐A expression reflected poor prognosis. The combination therapy with bevacizumab and navitoclax could significantly induce of cell death in vitro and reduce the tumour size and weight with well tolerated in vivo.

Conclusions

Our findings propose a novel combined strategy in which bevacizumab synergises with the BCL2 inhibitor venetoclax that is effective against B‐cell NHL.
Spatiotemporal expression pattern of PERIOD 1 and PERIOD 2 in the mouse SCN is dependent on VIP receptor 2 signaling
Authors: Hannibal Jens , Norn Tania H. B. , Georg Birgitte , Fahrenkrug Jan
Published: June 2019

Neurons of the hypothalamic suprachiasmatic nucleus (SCN) express clock genes, which regulate their own transcription and generate daily output signals driving circadian rhythmic behavior and physiology. The neuropeptide VIP and its specific receptor, the VPAC2 receptor, are important for synchronization of clock neurons. In the present study, we characterized PER1 and PER2 expressing neurons in wild‐type and VPAC2‐deficient mice. We found evidence for distinct spatiotemporal circadian oscillation in the expression of the PER genes in two separate clusters of SCN neurons. In wild‐type mice corresponding to the SCN shell and ventral core, high expression of PER was found at lights‐off most likely representing an evening clock (E‐clock). In another smaller cluster of neurons located in the central core of the SCN, PER expression peaks in antiphase at lights‐on and could represent a morning clock (M‐clock). BMAL1 immunoreactivity was found to be expressed in antiphase to PER in M and E neurons, respectively. PER was found in 98% of neurons expressing vasopressin (AVP) and in 92% of VIP neurons. The chemotype of M neurons was not identified. M but not E cells were responsive to long but not short photoperiods. The expression of the VPAC2 receptor was found in both M and E cells, and VPAC2‐deficient mice displayed markedly blunted PER expression in both cell clusters of the SCN. Conclusion: These observations support the existence of M and E clocks involved in circadian and seasonal adaptation, which seem dependent on intact VIP/VPAC2 signaling in the SCN.
What single‐unit recording studies tell us about the basic mechanisms of sleep and wakefulness
Authors: Sakai Kazuya
Published: June 2019

This paper reviews the presence, localization and characteristics of state‐specific neurons in the mouse forebrain, midbrain and hindbrain that are involved in the control of ultradian sleep–wake cycles and shows that all these regions contain basic neural elements capable of generating the sleep–wake cycle. The chronic single‐unit recording method in unanaesthetized animals is useful for unravelling the dynamics of sleep–wake switching, in particular because it can analyse events at the level of single neurons, thereby decoding information used by the brain in determining its functional state. A prerequisite is to record a large number of all types of neurons, identify critical wake‐ and sleep‐promoting neurons and determine their activity profiles during the sleep–wake cycle and their trends in spike activity during the state transitions from wakefulness to sleep and from sleep to wakefulness in the same species. Here, I argue that single‐unit recordings in unanaesthetized mice help us to (a) determine key neural elements controlling sleep–wake dynamics, (b) elucidate the roles of forebrain and brainstem neurons in ultradian sleep–wake cyclicity and (c) gain a new insight into the functional significance of wakefulness, slow‐wave sleep and paradoxical (or rapid eye movement) sleep. I also discuss the merits and limitations of single‐unit recording compared with more recent genetic approaches, and I suggest that findings from studies using the classic electrophysiological technique will provide the foundation for future studies using new genetic techniques to dissect the neural networks responsible for the initiation, maintenance and cessation of each wake and sleep state.
When words hurt: Verbal suggestion prevails over conditioning in inducing the motor nocebo effect
Authors: Corsi Nicole , Emadi Andani Mehran , Sometti Davide , Tinazzi Michele , Fiorio Mirta
Published: June 2019

Perception and behavior are strongly influenced by the verbal information conveyed by other individuals (e.g., verbal suggestion) and by learning (e.g., conditioning). This influence is well represented by the placebo and nocebo effects, in which positive verbal suggestion associated with positive conditioning induces beneficial outcomes (placebo effect), while the opposite is true for the negative counterpart (nocebo effect). It is still unclear whether verbal suggestion and conditioning exert distinctive roles in influencing perception, behavior and motor system activity when they occur in opposite directions. To this purpose, fifty‐three healthy volunteers were assigned to four groups characterized by either congruent or incongruent verbal suggestion and conditioning. Participants were asked to perform a force motor task by pressing a piston as strongly as possible. Transcranial magnetic stimulation over the primary motor cortex was used to record motor evoked potentials (MEP) and cortical silent period (CSP) from the muscle involved in the task. We found that negative verbal suggestion counteracted positive conditioning and induced sense of weakness, effort, and force decrements. MEP amplitude was stable, whereas the CSP duration shortened in all the groups throughout the procedure, indicating the involvement of cortical inhibitory circuits, independently of the type of verbal suggestion or conditioning. Our findings highlight a prevalent role of verbal suggestion over conditioning in determining a worsening (nocebo effect) but not an improvement (placebo effect) of motor performance. These results suggest that words associated with treatments should be chosen carefully to avoid negative outcomes, especially in sports and clinical settings.
Deficiency, Contamination, and the Signal Processing Metaphor
Authors: Newton Paul E.
Published: June 2019

Educational assessment involves eliciting, transmitting, and receiving information concerning the level of proficiency of a learner in a specified domain. With that in mind, it is perhaps surprising that the literature seems to make very little use of the signal processing metaphor. The present article begins by making a general case for greater use of this metaphor, as a simple and intuitive thinking tool for helping to explain how educational assessment works. The main body of the article extends this argument by demonstrating the utility of the metaphor in helping to explain how educational assessment can go wrong. During the 1980s and 1990s, Samuel Messick extensively discussed two major ways in which educational assessment can go wrong via construct‐irrelevant variance and construct underrepresentation, respectively. Despite their importance, these concepts have had only a limited impact on the literature. Part of the reason for this may be a lack of clarity and comprehensiveness in their articulation. The present article aims to articulate these concepts more clearly and comprehensively, within a framework provided by the signal processing metaphor, reconfiguring them as signal contamination and signal deficiency, respectively.
Sulfasalazine decreases mouse cortical hyperexcitability
Authors: Alcoreza Oscar , Tewari Bhanu P. , Bouslog Allison , Savoia Andrew , Sontheimer Harald , Campbell Susan L.
Published: June 2019

Objective

Currently prescribed antiepileptic drugs (AEDs) are ineffective in treating approximately 30% of epilepsy patients. Sulfasalazine (SAS) is an US Food and Drug Administration (FDA)–approved drug for the treatment of Crohn disease that has been shown to inhibit the cystine/glutamate antiporter system xc‐ (SXC) and decrease tumor‐associated seizures. This study evaluates the effect of SAS on distinct pharmacologically induced network excitability and determines whether it can further decrease hyperexcitability when administered with currently prescribed AEDs.

Methods

Using in vitro cortical mouse brain slices, whole‐cell patch‐clamp recordings were made from layer 2/3 pyramidal neurons. Epileptiform activity was induced with bicuculline (bic), 4‐aminopyridine (4‐AP) and magnesium‐free (Mg2+‐free) solution to determine the effect of SAS on epileptiform events. In addition, voltage‐sensitive dye (VSD) recordings were performed to characterize the effect of SAS on the spatiotemporal spread of hyperexcitable network activity and compared to currently prescribed AEDs.

Results

SAS decreased evoked excitatory postsynaptic currents (eEPSCs) and increased the decay kinetics of evoked inhibitory postsynaptic currents (eIPSCs) in layer 2/3 pyramidal neurons. Although application of SAS to bic and Mg2+‐free–induced epileptiform activity caused a decrease in the duration of epileptiform events, SAS completely blocked 4‐AP–induced epileptiform events. In VSD recordings, SAS decreased VSD optical signals induced by 4‐AP. Co‐application of SAS with the AED topiramate (TPM) caused a significantly further decrease in the spatiotemporal spread of VSD optical signals.

Significance

Taken together this study provides evidence that inhibition of SXC by SAS can decrease network hyperexcitability induced by three distinct pharmacologic agents in the superficial layers of the cortex. Furthermore, SAS provided additional suppression of 4‐AP–induced network activity when administered with the currently prescribed AED TPM. These findings may serve as a foundation to assess the potential for SAS or other compounds that selectively target SXC as an adjuvant treatment for epilepsy.
Advancing research toward faster diagnosis, better treatment, and end of stigma in epilepsy
Authors: Pitkänen Asla , Henshall David C. , Cross J. Helen , Guerrini Renzo , Jozwiak Sergiusz , Kokaia Merab , Simonato Michele , Sisodiya Sanjay , Mifsud Janet
Published: June 2019

Seven large European Union (EU)–funded epilepsy‐related research projects joined forces in May 2018 in Brussels, Belgium, in a unique community building event—the epiXchange conference. During this conference, 170 investigators from the projects DESIRE, EpimiRNA, EPISTOP, EpiTarget, EpiXchange, and EpiPGX as well as the European Reference Network EpiCARE, met up with key stakeholders including representatives of the European Commission, patient organizations, commercial partners, and other European and International groups. The epiXchange conference focused on sharing and reviewing the advances made by each project in the previous 5 years; describing the infrastructures generated; and discussing the innovations and commercial applications across five thematic areas: biomarkers, genetics, therapeutics, comorbidities, and biobanks and resources. These projects have, in fact, generated major breakthroughs including the discovery of biofluid‐based molecules for diagnosis, elucidating new genetic causes of epilepsy, creating advanced new models of epilepsy, and the pre‐clinical development of novel compounds. Workshop‐style discussions focused on how to overcome scientific and clinical challenges for accelerating translation of research outcomes and how to increase synergies between the projects and stakeholders at a European level. The resulting advances would lead toward a measurable impact of epilepsy research through better diagnostics, treatments, and quality‐of‐life for persons with epilepsy. In addition, epiXchange provided a unique forum for examining how the different projects could build momentum for future novel groundbreaking epilepsy research in Europe and beyond. This report includes the main recommendations that resulted from these discussions.
Cuckoo and krill herd‐based k‐means++ hybrid algorithms for clustering
Authors: Aggarwal Shruti , Singh Paramvir
Published: June 2019

Clustering algorithms can be optimized using nature‐inspired techniques. Many algorithms inspired by nature, namely, firefly algorithm, ant colony optimization algorithm, and so forth, have improved clustering results. k‐means is a popular clustering technique but has limitations of local optima, which have been overcome using its various hybrids. k‐means++ is a hybrid k‐means clustering algorithm that gives the procedure to initialize centre of the clusters. In the proposed work, hybrids of nature‐inspired techniques using cuckoo and krill herd algorithm are implemented on k‐means++ algorithm to enhance cluster quality and generate optimized clusters. The designed algorithms are implemented, and the results are compared with their counterparts. Performance parameters such as accuracy, f‐measure, error rate, standard deviation, CPU time, cluster quality check, and so forth are used to measure the clustering capabilities of these algorithms. The results indicate the high performance of newly designed algorithms.
Wearable ECG signal processing for automated cardiac arrhythmia classification using CFASE‐based feature selection
Authors: Zhang Yuwei , Zhang Yuan , Lo Benny , Xu Wenyao
Published: June 2019

Classification of electrocardiogram (ECG) signals is obligatory for the automatic diagnosis of cardiovascular disease. With the recent advancement of low‐cost wearable ECG device, it becomes more feasible to utilize ECG for cardiac arrhythmia classification in daily life. In this paper, we propose a lightweight approach to classify five types of cardiac arrhythmia, namely, normal beat (N), atrial premature contraction (A), premature ventricular contraction (V), left bundle branch block beat (L), and right bundle branch block beat (R). The combined method of frequency analysis and Shannon entropy is applied to extract appropriate statistical features. Information gain criterion is employed to select features that the results show that 10 highly effective features can obtain performance measures comparable to those obtained by using the complete features. The selected features are then fed to the input of Random Forest, K‐Nearest Neighbour, and J48 for classification. To evaluate classification performance, tenfold cross validation is used to verify the effectiveness of our method. Experimental results show that Random Forest classifier demonstrates significant performance with the highest sensitivity of 98.1%, the specificity of 99.5%, the precision of 98.1%, and the accuracy of 98.08%, outperforming other representative approaches for automated cardiac arrhythmia classification.
Multistakeholder initiatives in global production networks: naturalizing specific understandings of sustainability through the Better Cotton Initiative
Authors: RIISGAARD LONE , LUND‐THOMSEN PETER , COE NEIL M.
Published: June 2019

In recent years, various academics, consultants, companies and NGOs have advocated a move towards more cooperative approaches to private sustainability standards to address the widely identified shortcomings of the compliance paradigm. However, is it possible to address these limitations by moving towards stakeholder inclusion and capacity building while at the same time catering to the demands of lead firms supplying the mainstream market? In this article, we analyse how the Better Cotton Initiative (BCI) seeks to do just that, in the process identifying three key tensions and competing policy concerns with which standard‐setters have had to grapple – (a) stakeholder inclusion vs process‐control/efficiency; (b) stringency of the standard vs scale of production; and (c) capacity building vs auditing. Combining theoretical considerations about governance in global production networks (GPNs) with a convention theory perspective, we explore these inherent tensions and show that due to pre‐existing power relations in the cotton GPN, it is hard to develop more cooperative approaches because market and industrial values tend to win out despite efforts to follow current best practice on sustainability standard‐setting.
Efficacy and safety of glecaprevir/pibrentasvir as retreatment therapy for patients with genotype 2 chronic hepatitis C who failed prior sofosbuvir plus ribavirin regimen
Authors: Kusakabe Atsunori , Kurosaki Masayuki , Itakura Jun , Joko Kouji , Akahane Takehiro , Tsuji Keiji , Kobashi Haruhiko , Sohda Tetsuro , Kimura Hiroyuki , Narita Ryouichi , Furuta Koichirou , Izumi Namiki
Published: June 2019

Aim

Rescue therapy for patients with genotype 2 (GT2) chronic hepatitis C who failed prior sofosbuvir (SOF) plus ribavirin (RBV) awaits establishment. This study aims to investigate the efficacy and safety of the fixed‐dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB) for patients with GT2 chronic hepatitis C.

Methods

In this nationwide observational study undertaken by the Japanese Red Cross Liver Study Group, 28 GT2 patients with prior failure of SOF + RBV were retreated with GLE/PIB for 12 weeks. We evaluated the rate of sustained virologic response (SVR) and adverse events.

Results

After 4 weeks of therapy, serum hepatitis C virus RNA was below the limit of quantification in all patients. The SVR after 4 and 12 weeks of the end of treatment was validated in 100% (28/28) and 100% (28/28), respectively. The adverse events comprised pruritus (eight patients), fatigue (four patients), and appetite loss (four patients), all of which were mild in severity.

Conclusions

This study establishes the efficacy of GLE/PIB as retreatment in Japanese patients with GT2 chronic hepatitis C not responding to SOF + RBV.
Determining the thermal conductivity of ceramic coatings by relative method
Authors: Zheng Dezhi , Bao Yiwang , Wan Detian , Yi Shuai
Published: June 2019

Thermal conductivity is a crucial parameter for evaluating the quality and thermal effects of ceramic coatings, especially for thermal barrier coatings. However, measurement by conventional method involves two problems: (a) it is difficult to peel off a ceramic coating from a substrate; (b) even if the coating can be peeled off, it is still hardly used as standard specimen in test. Therefore, the relative method was proposed to evaluate the thermal conductivity of ceramic coating. An analytical relationship among the thermal conductivities of the coating, the substrate, and the coating/substrate composite was established. Experiments on TA4 coated with YSZ coatings were carried out to demonstrate the feasibility of this novel method and to investigate the impact of temperature on the thermal conductivity of YSZ coatings. The experimental results demonstrated the validity and convenience of the relative method. With the increasing testing temperature, the thermal conductivity value of YSZ coatings displayed nonlinearity feature, that is, decreased from 1.4 to 1.3 (W m−1 K−1) in the temperature range of 32‐300°C and then increased up to 1.58 W m−1 K−1 at 1000°C.
KIR specificity and avidity of standard and unusual C1, C2, Bw4, Bw6 and A3/11 amino acid motifs at entire HLA:KIR interface between NK and target cells, the functional and evolutionary classification of HLA class I molecules
Authors: Gwozdowicz Slawomir , Nestorowicz Klaudia , Graczyk‐Pol Elzbieta , Szlendak Urszula , Rogatko‐Koros Marta , Mika‐Witkowska Renata , Pawliczak Daria , Zubala Marta , Malinowska Agnieszka , Witkowska Agnieszka , Nowak Jacek
Published: June 2019

Natural killer (NK) cells make vital contributions to the immune system and the reproductive system. Notably, NK cells of donor origin can recognize and kill residual leukaemic cells and cure malignant patients in hematopoietic stem cell (HSC) transplant setting. NK cell function is regulated by KIRs that recognize cognate HLA class I molecules on target cells, depending on their amino acid residues. In review, we addressed the question of binding capacity and avidity of HLA class I molecules to different killer cell immunoglobulin‐like receptors (KIRs) depending on all interacting amino acid residues both on HLA and KIR side. We searched PubMed database and analysed available HLA:KIR crystallographic data for amino acid residues in HLA molecules, those physically involved in binding KIRs (termed here the “entire KIR interface”). Within entire KIR interface, we selected five functional sequence motifs (14–19, 66–76, 77–84, 88–92 and 142–151) and classified them according to the conservation of their amino acid sequences among 8,942 HLA class I molecules. Although some conserved amino acid motifs were shared by different groups of KIR ligands, the HLA motif combinations were exclusive for the ligand groups. In 135 common HLA class I molecules with known HLA:KIR recognition, we found 54 combinations of five motifs in each of the KIR‐binding interfaces (C1, C2, Bw4, A3/11) and conserved non‐KIR‐binding interfaces. Based on the entire KIR interface, this analysis allowed to classify 8,942 HLA class I molecules into KIR specificity groups. This functional and evolutionary classification of entire KIR interfaces provides a tool for unambiguously predicting HLA:KIR interactions for common and those HLA molecules that have not yet been functionally tested. Considering the entire KIR interface in HLA class I molecules, functional interactions of HLA and KIR can be predicted in immune responses, reproduction and allotransplantation. Further functional studies are needed on the HLA:KIR interaction variations caused by the repertoires of peptides presented by HLA molecules and KIR polymorphisms at allelic level.
Neurotoxicity in chronic lithium poisoning
Authors: Hlaing Phyu M. , Isoardi Katherine Z. , Page Colin B. , Pillans Peter
Published: June 2019

Background

Lithium‐induced neurotoxicity typically occurs with chronic accumulation rather than following acute overdose. There is little emphasis in the literature on the protracted nature of lithium neurotoxicity long after the lithium concentration returns to the therapeutic range.

Aims

To characterise lithium neurotoxicity, with a view of increasing awareness of this important phenomenon.

Methods

This is a retrospective observational study of patients presenting with lithium‐induced neurotoxicity over a 5‐year period to a clinical toxicology unit. Patients were identified through the unit's database, and clinical notes were analysed.

Results

There were 22 patients, with a median age of 65 (range: 36–89) years. Six patients (27%) had previous lithium toxicity, and nine (41%) were regularly prescribed medications that impair lithium excretion. The median lithium concentration on presentation was 2.2 mmol/L, taking a median of 3 days to return to the therapeutic range. Reversible acute kidney injury was observed in 21 patients (95%) on presentation. The median length of stay was 13 (range: 3–95) days due mostly to delayed neurological recovery. Confusion was the predominant symptom, present in 21 (95%) patients, followed by tremors (18(82%)) and ataxia (16(73%)). Multiple investigations were performed to exclude delirium differentials, including 11 computed tomography (CT) and five magnetic resonance imaging (MRI) brain scans, all unremarkable.

Conclusions

Lithium neurotoxicity has a prolonged course. Its severity correlates poorly with lithium concentrations, which normalise quickly. Most poisonings occur in elderly patients with acute kidney injury. Prolonged delirium often prompts multiple unnecessary investigations. Rationalisation of lithium therapy is important in elderly patients.
Prevalence and risk factors of ischaemic stroke in the young: a regional Australian perspective
Authors: Siriratnam Pakeeran , Godfrey Amelia , O’Connor Ellie , Pearce Dora , Hu Chih‐Chiang , Low Ashlea , Hair Casey , Oqueli Ernesto , Sharma Anand , Kraemer Thomas , Sahathevan Ramesh
Published: June 2019

Background

There is no universally accepted age cut‐off for defining young strokes.

Aims

We aimed to determine, based on the profile of young stroke patients in our regional centre, an appropriate age cut‐off for young strokes.

Methods

A retrospective analysis of all ischaemic stroke patients admitted to our centre from 2015 to 2017. We identified 391 ischaemic stroke patients; 30 patients between the ages of ≤50, 40 between 51–60 inclusive and 321 ≥ 61 years of age. We collected data on demographic profiles, risk factors and stroke classification using the Trial of Org 10 172 in Acute Stroke Treatment criteria.

Results

We found significant differences between the ≤50 and ≥61 age groups for most of the risk factors and similarities between the 51–60 inclusive and ≥ 61 age groups. At least one of the six risk factors assessed in the study was present in 86.7% of the youngest group, 97.5% of the intermediate age group and 97.2% in the oldest group. In terms of the mechanisms of stroke, the youngest and oldest age groups in our study differed in the prevalence of cryptogenic, cardioembolic and other causes of stroke. The middle and older age groups had similar mechanisms of stroke.

Conclusions

The prevalence of vascular risk factors and mechanisms of stroke likewise differed significantly across age groups. This study suggests that 50 years is an appropriate age cut‐off for defining young strokes and reinforces the importance of primary prevention in all age groups.
Long‐term outcomes in patients with pulmonary embolism: results from a longitudinal cohort study
Authors: Lamba Mehul , Pickering John W. , Than Martin , Iles Stephen , Beckert Lutz
Published: June 2019

Background

Patients with pulmonary embolism (PE) have increased mortality in short‐term; however, long‐term prognosis is not well defined.

Aim

In this long‐term cohort study, we aimed to determine if PE was associated with increased risk of mortality or serious clinical events (SCE). Secondary aims were to ascertain predictors of mortality and SCE.

Methods

Patients admitted with clinical suspicion of PE were prospectively recruited from July 2002 to May 2003 and followed up until March 2015. Clinical outcomes in patients with PE were compared to those without PE. SCE was defined as composite of mortality, malignancy, cardiovascular events, recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension.

Results

A total of 501 patients with median follow up of 11.9 years (interquartile range 3.91–12.28) was included. PE was diagnosed in 104 (20.7%) patients. Overall, 45.9% died and 57.1% developed SCE during follow up, with no significant difference in PE and no‐PE groups (both P > 0.5). Major determinants of mortality were age (hazard ratio (HR) 1.06 per year, 95% confidence interval (CI) 1.05–1.08), malignancy (HR 2.19, 95% CI 1.64–2.91) and congestive heart failure (HR 1.72, 95% CI 1.23–2.42). Factors associated with increased risk of SCE were age (HR 1.05 per year, 95% CI 1.04–1.06), malignancy (HR 1.93, 95% CI 1.48–2.52) and congestive heart failure (HR 1.77, 95% CI 1.29–2.43). In patients without PE, elevated D‐dimer concentration was not found to be associated with diagnosis of malignancy during follow up (HR 1.31, 95% CI 0.55–3.12).

Conclusions

In this prospective study, we did not find association between PE and risk of all‐cause mortality or SCE. Major determinants of poor clinical outcomes were advancing age and underlying comorbidities.
The psychological and social impact of self‐advocacy group membership on people with intellectual disabilities: A literature review
Authors: Fenn Kristina , Scior Katrina
Published: June 2019

Background

There is no one agreed definition of self‐advocacy, but it can be taken to include actions and concepts such as standing up for one's rights and self‐determination.

Method

A review of studies examining the psychological and social impact of self‐advocacy group membership on people with intellectual disabilities was conducted. Systematic searches of electronic databases (PsycINFO, Scopus, Web of Science and ProQuest's Sociology Database), and manual searches of reference lists and citations, identified 12 studies.

Results

“Empowerment” and “increased confidence” were frequently reported outcomes. “Belonging,” increased opportunities for social connections and changed self‐identity were also key themes.

Conclusions

Limitations of the review included difficulty categorizing outcomes, and limitations of the evidence base included a lack of quantitative studies. Implications of the review include an observation that the role of self‐advocates in the research literature could be extended to the co‐construction of research agendas.