bluuebunny/crossref_metadata_2025 huggingface dataset:
Population structure and geographically structured reproductive strategies of the haplodiplontic seaweedDictyota dichotoma
Authors: Steen Frédérique , Marc Verlaque , D’hondt Sofie , Vieira Christophe , Clerck Olivier De
Published: April 2019

Both mating system variation and the propensity of many seaweeds to reproduce both sexually and asexually, leave a strong imprint in the genetic structure of species. In this respect, we study the population genetic structure ofDictyota dichotoma, a common haplodiplont brown subtidal seaweed. This benthic species is widespread in the NE-Atlantic, from the Canary Islands and Mediterranean Sea to southern Norway, but lately populations have been reported from Argentina and South Africa. Phenology and reproduction ofD. dichotomawas monitored year-round in four populations to investigate how the species has adapted to the steep thermal gradient in southern and northern ranges of its distribution. Thirteen microsatellites are developed in order to assess patterns of population diversity and structure across the biogeographic range, as shaped by past and present processes. Last, we assess the genetic structure of South African and South American populations and their relationship to the northern hemisphere populations.

Throughout its range,D. dichotomashows a varying reproductive effort, with sexual reproduction being more abundant in the northern range. In contrast, the Mediterranean populations show a clear sporophyte dominance, suggesting that sexual reproduction is not the prime mode of reproduction, and indicating that the species potentially resorts to other modes of propagation as for instance fragmentation or apospory.

Genetic diversity is highest in the southern population decreasing gradually northward, indicative for a recolonization pattern after the demise of the last glacial maximum where these areas served as glacial refugia. European mainland populations show an isolation by distance pattern, while the population in the Canary Islands has its own genetic identity, being significantly diverged from the mainland population. Populations in South Africa and Argentina are seemingly introduced from mainland Europe, but no conclusion can be made on the exact timing of these introductions.
Dental abscesses on the maxilla of a two million-year-old earlyHomospecimen
Authors: Towle Ian , Irish Joel D.
Published: April 2019

Abscesses and other periapical lesions are found in abundance in recent archeological samples, yet are scarce in the fossil hominin record. Periapical voids commonly develop after exposure of a tooth’s pulp chamber and are commonly associated with heavy crown wear, trauma or caries. In this study, all available maxilla and mandible fragments from the South African fossil hominin collections were studied, including specimens assigned toHomo naledi, Paranthropus robustus, Australopithicus africanus, A. sedibaand earlyHomo. Only one specimen displayed voids consistent with periapical lesions, and a differential diagnosis of these voids was undertaken. The specimen, SK 847, is described as earlyHomoand has been dated to 2.3-1.65MA. There is one definite abscess, and likely at least two more with postmortem damage, all on the anterior aspect of the maxilla and associated with the incisors. The abscesses originate from the apices of the incisor roots and are therefore unlikely to represent a systemic disease such as multiple myeloma. They best fit the description of an abscess rather than a cyst or granuloma, with one showing a rounded thickened rim around the lesion. The abscesses highlight that this individual used their anterior dentition extensively, to the point that the pulp chambers were exposed on multiple teeth. This is one of the earliest hominin examples of a dental abscess and shows that this individual was able to cope with several concurrent abscesses, clearly surviving for an extended period. Therefore, this finding adds additional information to the history of dental pathology in our genus.
The FLAME-accelerated Signalling Tool (FaST): A tool for facile parallelisation of flexible agent-based models of cell signalling
Authors: Fullstone Gavin , Guttà Cristiano , Beyer Amatus , Rehm Markus
Published: April 2019

Agent-based modelling is particularly adept at modelling complex features of cell signalling pathways, where heterogeneity, stochastic and spatial effects are important, thus increasing our understanding of decision processes in biology in such scenarios. However, agent-based modelling often is computationally prohibitive to implement. Parallel computing, either on central processing units (CPUs) or graphical processing units (GPUs), can provide a means to improve computational feasibility of agent-based applications but generally requires specialist coding knowledge and extensive optimisation. In this paper, we address these challenges through the development and implementation of the FLAME-accelerated signalling tool (FaST), a software that permits easy creation and parallelisation of agent-based models of cell signalling, on CPUs or GPUs. FaST incorporates validated new agent-based methods, for accurate modelling of reaction kinetics and, as proof of concept, successfully converted an ordinary differential equation (ODE) model of apoptosis execution into an agent-based model. We finally parallelised this model through FaST on CPUs and GPUs resulting in an increase in performance of 5.8× (16 CPUs) and 53.9× respectively. The FaST takes advantage of the communicating X-machine approach used by FLAME and FLAME GPU to allow easy alteration or addition of functionality to parallel applications, but still includes inherent parallelisation optimisation. The FaST, therefore, represents a new and innovative tool to easily create and parallelise bespoke, robust, agent-based models of cell signalling.
Risk variant in miR-544a binding site in CCDC170 is associated with osteoporosis
Authors: Liu Xinhong , Wang Yang , Tan Qin , He Yunqi , Zhao Xin
Published: April 2019

MicroRNAs (miRNAs) play essential roles in regulating bone formation and homeostasis. Genomic variations within miRNA target sites may therefore be important sources of genetic differences in osteoporosis risk. To investigate this possibility, we searched for miRNA recognition sites within genes using the TargetScan, miRNASNP and miRbase databases. In this study, we showed that miR-544a differentially regulated the allele variants of rs6932603 in the CCDC170 3 ′ untranslated (3′-UTR). We also showed that miR-544a suppressed osteogenesis and promoted osteoclastogenesis by regulating the expressions of Runx2, Osterix, Alp, Col1a1, Osteopontin (OPN) ,Osteocalcin (OCN) and Osteoprotegerin (OPG). Our results suggest that allele-specific regulation of CCDC170 by miR-544a explains the observed disease risk, and provides a potential therapeutic target for osteoporosis therapy.
Projected changes of alpine grassland carbon dynamics in response to climate change and elevated CO2concentrations under Representative Concentration Pathways (RCP) scenarios
Authors: Han Pengfei , Lin Xiaohui , Zhang Wen , Wang Guocheng
Published: April 2019

The Tibetan Plateau is an important component of the global carbon cycle due to the large permafrost carbon pool and its vulnerability to climate warming. The Tibetan Plateau has experienced a noticeable warming over the past few decades and is projected to continue warming in the future. However, the direction and magnitude of carbon fluxes responses to climate change and elevated CO2concentration under Representative Concentration Pathways (RCP) scenarios in the Tibetan Plateau grassland are poorly known. Here, we used a calibrated and validated biogeochemistry model, CENTURY, to quantify the contributions of climate change and elevated CO2on the future carbon budget in the alpine grassland under three RCP scenarios. Though the Tibetan Plateau grassland was projected a net carbon sink of 16 ~ 25 Tg C yr-1in the 21st century, the capacity of carbon sequestration was predicted to decrease gradually because climate-driven increases in heterotrophic respiration (Rh) (with linear slopes 0.49 ~ 1.62 g C m-2yr-1) was greater than the net primary production (NPP) (0.35 ~ 1.52 g C m-2yr-1). However, the elevated CO2contributed more to plant growth (1.9% ~ 7.3%) than decomposition (1.7% ~ 6.1%), which could offset the warming-induced carbon loss. The interannual and decadal-scale dynamics of the carbon fluxes in the alpine grassland were primarily controlled by temperature, while the role of precipitation became increasingly important in modulating carbon cycle. The strengthened correlation between precipitation and carbon budget suggested that further research should consider the performance of precipitation in evaluating carbon dynamics in a warmer climate scenario.
Preparation of Polymerase Chain Reaction Template DNA from Mouse Tail Tissue
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: April 2019

A simple cell or tissue lysate can provide a sufficient quality and amount of template DNA for polymerase chain reaction (PCR). In this protocol, a small piece from the tip of the tail is removed and processed using hot sodium hydroxide and Tris (HotSHOT).
Detecting Alkaline Phosphatase–Labeled Cells
Authors: Rodig Scott J.
Published: April 2019

Different substrates are available for detection of cells labeled with alkaline phosphatase. Naphthol-AS-BI-phosphate (NABP)/New Fuchsin produces an intense red product that is insoluble in alcohols as well as aqueous solutions and is compatible with a range of histochemical stains. Bromochloroindoyl phosphate/nitro blue tetrazolium (BCIP/NBT) is the most commonly used of the chromogenic substrates for alkaline phosphatase. It is somewhat more sensitive than NABP/New Fuchsin but gives less contrast during microscopic observation.
Mapping Chromatin Features of Xenopus Embryos
Authors: Gentsch George E. , Smith James C.
Published: April 2019

Chromatin immunoprecipitation (ChIP) combined with genomic analysis provides a global snapshot of protein–DNA interactions in the context of chromatin, yielding insights into which genome loci might be regulated by the DNA-associated protein under investigation. This protocol is an update of a previous version and describes how to perform ChIP on intact or dissected Xenopus embryos. The ChIP-isolated DNA fragments are suitable for both deep sequencing (ChIP-Seq) and quantitative polymerase chain reaction (ChIP-qPCR). General advice for qPCR and for making ChIP-Seq libraries is offered, and approaches for analyzing ChIP-Seq data are outlined.
RNA Interference and Small RNA Analysis
Authors: Li Chengjian , Zamore Phillip D.
Published: April 2019

Small silencing RNAs have provided powerful reverse genetics tools and have opened new areas of research. This introduction describes the use of RNAi to suppress expression of individual genes for loss-of-function analysis. It also summarizes methods for measuring specific and global changes in small RNA expression, as well as methods to inhibit the function of individual endogenous small RNA species such as miRNAs.
Factors affecting the unplanned use behavior of academic libraries users
Authors: Harati Hadi , Nooshinfard Fatemeh , Isfandyari-Moghaddam Alireza , Babalhavaeji Fahimeh , Hariri Nadjla
Published: April 2019

Purpose

The purpose of this paper is to identify and design the axial coding pattern of the factors affecting the unplanned use behavior of users of the academic libraries and information centers.

Design/methodology/approach

The study as an applied research with a qualitative approach employed the grounded theory. The data collection tool was a deep and semi-structured interview. The interviews data were analyzed and coded during three stages of open, axial and selective coding using the MAXQDA 10 qualitative analysis software. The research population consisted of faculty members and experts in three areas of library and information science, management and psychology. Using the combined targeted sampling method (targeted and then the snowball), 12 subjects were selected as the sample size.

Findings

According to the research findings, the factors affecting the unplanned behavior of users in the use of academic libraries resources and services were identified as factors related to technology, environmental factors, information resources, information services, human resources, individual features, time position factor, cultural factors and social factors. Accordingly, the axial coding pattern of this type of behaviors was designed.

Research limitations/implications

The research limitations include the lack of theoretical basis related to the unplanned behavior issue in the field of library and information science and the lack of full familiarity of most of the experts in the field of library and information science with this topic. These factors lead to the necessity of explaining the subject under discussion.

Originality/value

The unplanned behavior of clients can be utilized to persuade users to use the information resources and library services so that the costs spent on their preparation and collection will be justifiable. The current research addressed this aspect of the unplanned information-seeking behavior.
Performance improvement of direct torque control for induction motor drive via fuzzy logic-feedback linearization
Authors: Ammar Abdelkarim
Published: April 2019

Purpose

This paper aims to propose an improved direct torque control (DTC) for the induction motor’s performance enhancement using dual nonlinear techniques. The exact feedback linearization is implemented to create a linear decoupled control. Besides, the fuzzy logic control approach has been inserted to generate the auxiliary control input for the feedback linearization controller.

Design/methodology/approach

To improve the DTC for induction motor drive, this work suggests the incorporation of two nonlinear approaches. As the classical feedback linearization suffers while the presence of uncertainties and modeling inaccuracy, it is recommended to be associated to another robust control approach to compensate the uncertainties of the model and make a robust control versus the variations of the machine parameters. Therefore, fuzzy logic controllers will be integrated as auxiliary inputs to the feedback linearization control law.

Findings

The simulation and the experimental validation of the proposed control algorithm show that the association of dual techniques can effectively achieve high dynamic behavior and improve the robustness against parameters variation and external disturbances. Moreover, the space vector modulation is used to preserve a fixed switching frequency, reduce ripples and low switching losses.

Practical implications

The theoretical, simulation and experimental studies prove that the proposed control algorithm can be used on different AC machines for variable speed drive applications such as oil drilling, traction systems and wind energy conversion systems.

Originality/value

The proposed DTC strategy has been developed theoretically and realized through simulation and experimental implementation. Different operation conditions have been conducted to check the ability and robustness of the control strategy, such as steady state, speed reversal maneuver, low-speed operation and parameters variation test with load application.
Effect of high frequency harmonic voltage on the performance of line start permanent magnet synchronous motor
Authors: Qiu Hongbo , Hu Kaiqiang , Yi Ran , Yanqi Wei
Published: April 2019

Purpose

A large number of high-frequency harmonic voltages exist in the output voltage of the inverter, which will affect the performance of the motor. The purpose of this paper is to obtain the influence of high frequency harmonic voltage on the performance of the line start permanent magnet synchronous motor (LSPMSM) and reveal the mechanism of influence. The research results can provide help for the design of LSPMSM driven by inverter drives.

Design/methodology/approach

First, the actual output voltage data of the inverter is collected, and then the fundamental voltage and high frequency harmonic voltage data can be obtained by performing the fast Fourier transformation method on the voltage data. Second, the finite element model is established. During the finite element calculation, the obtained fundamental voltage and the main harmonic voltage components are used as the voltage source. To research the effect of high frequency harmonic voltage on the performance of motor, a reference group without high frequency harmonic voltage is set up, which is used to compare and analyze the effect of high-frequency harmonics on the performance of the motor. To verify the correctness of the model, a prototype based on the model parameters is manufactured, and then the back EMF experiment and load experiment are performed. The test data and calculation results are compared and analyzed.

Findings

The coupling relationship between high frequency time harmonic magnetic field and low frequency space harmonic magnetic field is obtained. The stator copper loss and rotor eddy-current loss are calculated and analyzed under normal supply voltage and abnormal supply voltage, and the influence mechanism is revealed

Originality/value

The coupling relationship between high frequency time harmonic magnetic field and low frequency space harmonic magnetic field is obtained. The sensitivity of the high frequency harmonic voltage to the stator copper loss and rotor eddy-current loss is obtained, and the mechanism of losses change is revealed.
Modeling of electrical behavior of undoped symmetric Double-Gate (DG) MOSFET using carrier-based approach
Authors: Singh Ajay Kumar
Published: April 2019

Purpose

This study aims to develop a compact analytical models for undoped symmetric double-gate MOSFET based on carrier approach. Double-Gate (DG) MOSFET is a newly emerging device that can potentially further scale down CMOS technology owing to its excellent control of short channel effects, ideal subthreshold slope and free dopant-associated fluctuation effects. DG MOSFET is of two types: the symmetric DG MOSFET with two gates of identical work functions and asymmetric DG MOSFET with two gates of different work functions. To fully exploit the benefits of DG MOSFETs, the body of DG MOSFETs is usually undoped because the undoped body greatly reduces source and drain junction capacitances, which enhances the switching speed. Highly accurate and compact models, which are at the same time computationally efficient, are required for proper modeling of DG MOSFETs.

Design/methodology/approach

This paper presents a carrier-based approach to develop a compact analytical model for the channel potential, threshold voltage and drain current of a long channel undoped symmetric DG MOSFETs. The formulation starts from a solution of the 2-D Poisson’s equation in which mobile charge term has been included. The 2-D Poisson’s equation in rectangular coordinate system has been solved by splitting the total potential into long-channel (1-D Poisson’s equation) and short-channel components (remnant 2-D differential equation) in accordance to the device physics. The analytical model of the channel potential has been derived using Boltzmann’s statistics and carrier-based approach.

Findings

It is shown that the metal gate suppresses the center potential more than the poly gate. The threshold voltage increases with increasing metal work function. The results of the proposed models have been validated against the Technology Computer Aided Design simulation results with close agreement.

Originality/value

Compact Analytical models for undoped symmetric double gate MOSFETs.
Walk the talk: soft skills’ assessment of graduates
Authors: Succi Chiara , Wieandt Michaela
Published: April 2019

Purpose

A fast-changing environment entails several reflections about skills and attitudes required to face the increasing complexity brought by the “glocal, liquid and networked” world in which workers operate (Bauman, 2003; Clarke, 2017). In the literature, an increased attention has been devoted to the impact of interpersonal skills and personal characteristics on employability (Heckman and Kautz, 2012; Succi, 2019; Wheeler, 2016). In this context, the so-called soft skills become of crucial importance, but a lack of academic attention devoted to their development, and a deficit of companies in integrating soft skills in their selection, induction and training processes have been identified (Hurrell, 2016). The paper aims to discuss these issues.

Design/methodology/approach

An exploratory study has been designed to describe the tools in use to assess soft skills, during the recruitment process and those to develop soft skills of graduates, during their first years on the job. In January 2017, two symmetrical online questionnaires have been sent to 500 HR managers and 240 graduates of a European business school, in Italy and Germany.

Findings

Results show that graduates and managers describe differently the use of tools to develop graduates’ soft skills. The large majority of HR managers indicate they offer formal training to young graduates and that they are involved in the performance appraisal sessions, while only 22 percent of students confirm they receive formal training and only 26 percent declare to be inserted in a performance appraisal process. Moreover, concerning the assessment of soft skills during the selection process, significant differences between Italian and German companies emerged.

Research limitations/implications

This research constitutes the first step to acknowledge the lack of initiatives devoted to soft skills development, despite their rising importance for the job market.

Practical implications

Findings allow initiating a discussion about a strategic topic in human resources management: whose responsibility is it to develop soft skills? Should graduates, higher education or companies fill the gap? The study can be extended to other types of higher education institutions, and a qualitative research could deepen the understanding of root causes of the differences identified.

Social implications

The impact on youth employment, reduction of labor skills mismatch and improvement of managerial practices could be interesting social implications of the study.

Originality/value

While previous research has predominantly focused on higher education executives and HR managers, this paper’s contribution consists in involving young graduates in the reflection on employability.
Therapeutic potential of medicinal plants for the management of urinary tract infection: A systematic review
Authors: Shaheen Ghazala , Akram Muhammad , Jabeen Farhat , Ali Shah Syed Muhammad , Munir Naveed , Daniyal Muhammad , Riaz Muhammad , Tahir Imtiaz Mahmood , Ghauri Aymen Owais , Sultana Sabira , Zainab Rida , Khan Muslim
Published: April 2019

Urinary tract infection (UTI) is one of the most severe public health problem affecting both sexes but females are more susceptible due to the differences in urogenital and reproductive anatomy, physiology and lifestyle. As in UTI, different parts of the urinary tract are affected and morbidity due to UTI is more common in women of all ages and older men. Due to multi‐drug resistant strains and high recurrence rate, UTI has become a major socioeconomic burden. The current review article was aimed to describe the natural therapeutic strategies to manage and cure the UTI. For this purpose, different databases including Google Scholar, Cochrane database, and PubMed etc. were explored. Inclusion criteria were any research article investigating the current therapy of UTI. It was found that microbial infections including Escherichia coli, Enterococcus faecalis and Klebsiella species are the major causes of UTI with different signs and symptoms including painful urination or dysuria, hematuria, urinary urgency, burning micturition, frequent urination, nausea, and vomiting. Antibiotics like trimethoprim, sulfamethoxazole, quinolone etc. as the first choice of the drug are used worldwide. However, due to microbial resistance, several life‐threatening side effects, repeated high doses, high cost and low efficacy of these antibiotics motivated the researchers to explore natural remedies for the treatment of UTI. Herbal medicines are effective to combat bacterial resistance with high efficacy, and easy availability with minimal or no side effects. For these reasons it has attained the attention of researchers wanting to explore the herbal treatment of UTI. Vaccinium macrocarpon, Tribulus terrestris, Trachyspermum copticum, Cinnamomum verum and Hybanthusenn easpermus are some common medicinal plants reported to have therapeutic potential for the management and cure of the UTI. Although herbal medicines have more potential over conventional medicine but more discoveries are required to explore the phytoconstituents and their mechanism of action responsible for the management and cure of UTI.
Holding the wild in the seed: Place, escape and liminality at the Millennium Seed Bank Partnership
Authors: LEWIS‐JONES KAY E.
Published: April 2019

The Millennium Seed Bank Partnership (MSBP), which conserves the seeds of wild plants, is the world's largestex situplant conservation project. Recourse toex situconservation, however, presents something of a paradox for the conservation of plants. Plant ecology often defies delineation into distinct units and is intricately rooted in place. ‘Plant‐being’, therefore, has elicited attention within the ‘more‐than‐human’ turn for its entangled and relational nature. Yet, as the author considers here through reference to her research within the MSBP, in the context of seed conservation, survival for plant species is pursued precisely through escaping place and entanglement. By ‘thinking‐with’ seed ecology, she proposes that a dialectic between plant and seed – and thus between entanglement and disentanglement – emerges, suggesting that rather than presenting a paradox, the practice of seed conservation might potentially foster a liminal, generative and experimental space within which new formations of human‐plant relationships might be nurtured.
The Agricultural Land Market in the EU and the Case for Better Data Provision
Authors: Loughrey Jason , Donnellan Trevor , Hanrahan Kevin
Published: April 2019

Participants in agricultural land markets require comprehensive statistics in order to make informed decisions in relation to agricultural land and the associated production. The publication of such data supports land mobility, the competitiveness and generational renewal of the sector. This article describes the functioning of agricultural land markets in EU Member States and the associated data infrastructure. We identify a scarcity of information regarding the volume of land sales transactions but significant recent improvements in the reporting of comparable statistics on agricultural land sales prices. Wide disparities between Member States both in terms of their agricultural land sales and agricultural land rental markets are documented. There remain significant data gaps in terms of land rental prices in EU Member States. Further EU‐wide research should be carried out in relation to land rental price indices with adjustments for the underlying land characteristics. The resulting price indices should provide a better indication of the competitiveness of land markets in EU regions. Finally, the analysis identifies recent improvements in measuring the extent of land fragmentation in the EU but finds that this analysis is confined to a minority of Member States.
The TotaltrackTM video laryngeal mask: an evaluation in 300 patients
Authors: Gómez‐Ríos M. Á. , Freire‐Vila E. , Casans‐Francés R. , Pita‐Fernández S.
Published: April 2019

The TotaltrackTM is a new video laryngeal mask, which combines a supraglottic airway with a videolaryngoscope. We evaluated the performance of this device in an observational study in 300 adult patients. The Totaltrack was inserted at the first attempt and the glottis seen in all cases. In 249 patients (83%; 95%CI 78.7–87.3%) the glottis was seen at the first attempt. Adequate ventilation and tracheal intubation were achieved in all patients. The median time to visualisation of vocal cords, to confirmation of ventilation and to successful tracheal intubation was 5 s, 13 s and 24 s, respectively. Nineteen patients (6.3%; 95%CI 3.55–9.05%) suffered minor complications, such as mucosal lesion or blood staining. The Totaltrack appears effective for airway management.
The development of an extended normothermic ex vivo reperfusion model of the sheep uterus to evaluate organ quality after cold ischemia in relation to uterus transplantation
Authors: Padma Arvind M. , Truong MyLan , Jar‐Allah Tagrid , Song Min J. , Oltean Mihai , Brännström Mats , Hellström Mats
Published: April 2019

Introduction

Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor‐intensive in vivo transplantation experiments.

Material and methods

Isolated sheep uteri were perfused with the preservation solution IGL‐1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury.

Results

Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic‐labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH.

Conclusions

We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury‐related differences associated to organ preservation. The experimental setup is a platform that can be used to conduct further studies on uterine ischemia‐ and reperfusion injury that may lead to improved human uterus transplantation protocols.
Consensus report: clinical recommendations for the prevention and management of the nocebo effect in biosimilar‐treated IBD patients
Authors: Pouillon Lieven , Danese Silvio , Hart Ailsa , Fiorino Gionata , Argollo Marjorie , Selmi Carlo , Carlo‐Stella Carmelo , Loeuille Damien , Costanzo Antonio , Lopez Anthony , Vegni Elena , Radice Simona , Gilardi Daniela , Socha Marie , Fazio Maria , González‐Lorenzo Marien , Bonovas Stefanos , Magro Fernando , Peyrin‐Biroulet Laurent
Published: April 2019

Background

The nocebo effect is a negative effect of a pharmacological or nonpharmacological medical treatment that is induced by patients' expectations, and that is unrelated to the physiological action of the treatment. The nocebo effect can negatively affect treatment outcomes.

Aim

To develop evidence‐based consensus recommendations for the prevention and management of the nocebo effect in biosimilar‐treated patients with IBD.

Methods

The “NOCE‐BIO Consensus Group” was composed of 19 members from five European countries, and with different fields of expertise. A literature review on the nocebo effect, with specific focus on information about its prevention and management in biosimilar‐treated IBD patients, was performed. Preliminary statements were formulated and voted on during a consensus group meeting held in Milan, Italy, in July 2018. A statement was accepted if >75% of participants voted 4 (“agree”) or 5 (“strongly agree”) on a scale of 1‐5.

Results

Consensus was reached on 11 recommendation statements. Seven statements reached consensus after one voting round and four statements reached consensus after two voting rounds. All statements were supported by very low‐quality level of evidence. The panel agreed that patient‐health‐care provider relationship is a key driver of acceptance of biosimilars, which limits the risk of negative bias and the nocebo effect. Lack of knowledge among patients and health‐care providers about the effectiveness and safety of biosimilars should be minimized. Education about biosimilars needs to be tailored to the individual patient, and positive framing is recommended.

Conclusions

The nocebo effect is under‐recognised in the era of biosimilars, although it may negatively impact on the cost‐savings of biosimilars. Future research should focus on the magnitude, the risk factors, the impact, and the management of the nocebo effect in biosimilars‐treated IBD patients.
Warfarin dose requirement in patients having severe thrombosis or thrombophilia
Authors: Helin Tuukka A. , Joutsi‐Korhonen Lotta , Asmundela Heidi , Niemi Mikko , Orpana Arto , Lassila Riitta
Published: April 2019

Aims

Warfarin dose requirement varies significantly. We compared the clinically established doses based on international normalized ratio (INR) among patients with severe thrombosis and/or thrombophilia with estimates from genetic dosing algorithms.

Methods

Fifty patients with severe thrombosis and/or thrombophilia requiring permanent anticoagulation, referred to the Helsinki University Hospital Coagulation Center, were screened for thrombophilias and genotyped for CYP2C9*2 (c.430C>T, rs1799853), CYP2C9*3 (c.1075A>C, rs1057910) and VKORC1 c.‐1639G>A (rs9923231) variants. The warfarin maintenance doses (target INR 2.0–3.0 in 94%, 2.5–3.5 in 6%) were estimated by the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) algorithms. The individual warfarin maintenance dose was tailored, supplementing estimates with comprehensive clinical evaluation and INR data.

Results

Mean patient age was 47 years (range 20–76), and BMI 27 (SD 6), 68% being women. Forty‐six (92%) had previous venous or arterial thrombosis, and 26 (52%) had a thrombophilia, with 22% having concurrent aspirin. A total of 40% carried the CYP2C9*2 or *3 allele and 54% carried the VKORC1‐1639A allele. The daily mean maintenance dose of warfarin estimated by the Gage algorithm was 5.4 mg (95% CI 4.9–5.9 mg), and by the IWPC algorithm was 5.2 mg (95% CI 4.7–5.7 mg). The daily warfarin maintenance dose after clinical visits and follow‐up was higher than the estimates, mean 6.9 mg (95% CI 5.6–8.2 mg, P < 0.006), with highest dose in patients having multiple thrombophilic factors (P < 0.03).

Conclusions

In severe thrombosis and/or thrombophilia, variation in thrombin generation and pharmacodynamics influences warfarin response. Pharmacogenetic dosing algorithms seem to underestimate dose requirement.
Sociotechnical co‐evolution of an e‐Learning innovation network
Authors: Law Nancy , Liang Leming
Published: April 2019

This paper reports on a longitudinal study of a network of 10 special education needs schools over a span of 11 years that leveraged the opportunity offered by a government‐funded e‐learning pilot scheme initiative to further their efforts in providing the same educational opportunities to their students as those in mainstream schools. The trajectory of this network’s evolution shows that its robustness lies in the joint leadership network among the schools, and the insight and agency that this leadership network exhibited in the intentional exploration and crafting of a social structure and mechanism to support innovative developments in technology and pedagogical innovation, which we refer to as sociotechnical co‐evolution. By adopting a sociotechnical system framework to analyse the changes at the landscape, regime and niches levels, we show that in fact landscape factors play a crucial role in shaping the innovation trajectory through its influence on the niches. Network leadership, within‐school leadership and organizational infrastructures evolve and play an important role in the co‐construction of the sociotechnical regimes needed to bring about deep and widespread changes in pedagogical practice.
Meeting players where they are: Digital games and learning ecologies
Authors: Persico Donatella , Passarelli Marcello , Pozzi Francesca , Earp Jeffrey , Dagnino Francesca Maria , Manganello Flavio
Published: April 2019

This paper explores the relationship between digital games and learning along the continuum from formal to informal learning. Games are an increasingly important component of our learning ecologies but their potential can prove difficult to fully harness due to the downsides of gaming in informal contexts and to the limitations games can present when adopted in formal learning contexts. The aim of this paper is to shed light on the strengths and weaknesses of games for learning, and to gather stakeholder recommendations for the main actors in the field. The adopted research approach is qualitative and participatory, involving players, teachers, parents, researchers and developers. Data from 25 interviews and 11 focus groups yielded insights into the educational, psychological and ethical aspects of play. Results suggest that gameplay influences individuals in a very personal manner, and that its effects cover a wide range of skills, extending to identity development. Hence, to harness this potential, all actors in the ecology need strong awareness of both the affordances and the risks of games, and deep respect for individuals’ LEs. The study has implications for a wide range of actors, including educators, players, researchers, parents, game developers and policymakers.
Integrating games as a means to develop e‐learning: Insights from a psychological perspective
Authors: Terras Melody M. , Boyle Elizabeth A.
Published: April 2019

Although the Education sector has pioneered the use of technology, the pace of technological change has outstripped the slower processes of theoretical development and critical reflection, so the field is highly fragmented and lacks a comprehensive evidence base to support future development. In this paper, we consider how the insights offered by games and a psychological perspective can address the current challenges. Both games and e‐learning specialists are facing similar challenges and would therefore benefit from adopting a more integrated approach in the future. We demonstrate how this integration can best be achieved by viewing the challenges through a psychological lens which informs theory, research and practice in user‐centred design, supports the development of more widely applicable theories of learning and pedagogy, recognises of the complexity of the contexts in which learning occurs and offers an established evidence‐based framework to aid integration at the theoretical level. This emphasises the continued importance of classic concepts such as transfer, cognitive load and the increasing blurred boundaries between formal and informal learning, but also in terms of methodology and as a catalyst for future debate and discussion.
Profiles of adversity and resilience resources: A latent class analysis of two samples
Authors: Lines Robin L. J. , Crane Monique , Ducker Kagan J. , Ntoumanis Nikos , Thøgersen‐Ntoumani Cecilie , Fletcher David , Gucciardi Daniel F.
Published: April 2019

Adversities refer to events that are characterized by perceived or actual threat to human functioning. Often considered deleterious for health and well‐being, recent work supports an alternative picture of the effects of adversity on human functioning, such that a moderate amount of adversity – when compared with none or high levels – can be beneficial. We extend this body of work in the current study by considering the breadth or type of adversities experienced simultaneously (referred to as polyadversity), with a focus on individual profiles of lifetime adversities. Latent class analysis was employed to explore different configurations of lifetime adversity experiences in two independent samples and examine how these latent classes differed with regard to resilience resources (i.e., optimism, hope, self‐efficacy, and bounce‐back ability). University students (N = 348) and members from the broader community (N = 1,506) completed measures of lifetime adversity exposure and resilience resources. Three polyadversity classes were revealed in each sample, with both producing a high and a low polyadversity class. The third class differed between samples; in the student sample, this class represented experiences of vicarious adversity, whereas in the community sample, it represented moderate levels of exposure to adversity. Support for the adaptive nature of a moderate amount of adversity exposure was found in the community sample but not in the student sample. This study produces initial evidence of how lifetime adversity experiences group together and how class membership is related to resilience resources.
Courts, care proceedings and outcomes uncertainty: The challenges of achieving and assessing “good outcomes” for children after child protection proceedings
Authors: Dickens Jonathan , Masson Judith , Garside Ludivine , Young Julie , Bader Kay
Published: April 2019

The professed aim of any social welfare or legal intervention in family life is often to bring about “better outcomes for the children.” But there is considerable ambiguity about “outcomes,” and the term is far too often used in far too simplistic a way. This paper draws on empirical research into the outcomes of care proceedings for a randomly selected sample of 616 children in England and Wales, about half starting proceedings in 2009–2010 and the others in 2014–2015. The paper considers the challenges of achieving and assessing “good outcomes” for the children. Outcomes are complex and fluid for all children, whatever the court order. One has to assess the progress of the children in the light of their individual needs and in the context of “normal” child development, and in terms of the legal provisions and policy expectations. A core paradox is that some of the most uncertain outcomes are for children who remain with or return to their parents; yet law and policy require that first consideration is given to this option. Greater transparency about the uncertainty of outcomes is a necessary step towards better understanding the risks and potential benefits of care proceedings.
Example‐Based Colourization Via Dense Encoding Pyramids
Authors: Xiao Chufeng , Han Chu , Zhang Zhuming , Qin Jing , Wong Tien‐Tsin , Han Guoqiang , He Shengfeng
Published: April 2019

We propose a novel deep example‐based image colourization method called dense encoding pyramid network. In our study, we define the colourization as a multinomial classification problem. Given a greyscale image and a reference image, the proposed network leverages large‐scale data and then predicts colours by analysing the colour distribution of the reference image. We design the network as a pyramid structure in order to exploit the inherent multi‐scale, pyramidal hierarchy of colour representations. Between two adjacent levels, we propose a hierarchical decoder–encoder filter to pass the colour distributions from the lower level to higher level in order to take both semantic information and fine details into account during the colourization process. Within the network, a novel parallel residual dense block is proposed to effectively extract the local–global context of the colour representations by widening the network. Several experiments, as well as a user study, are conducted to evaluate the performance of our network against state‐of‐the‐art colourization methods. Experimental results show that our network is able to generate colourful, semantically correct and visually pleasant colour images. In addition, unlike fully automatic colourization that produces fixed colour images, the reference image of our network is flexible; both natural images and simple colour palettes can be used to guide the colourization.
Adjunctive efficacy of diode laser in the treatment of peri‐implant mucositis with mechanical therapy: A randomized clinical trial
Authors: Aimetti Mario , Mariani Giulia Maria , Ferrarotti Francesco , Ercoli Elena , Liu Chun Ching , Romano Federica
Published: April 2019

Objectives

Due to the inconclusive findings on the effect of laser therapy in the management of peri‐implant diseases, the aim of this study was to analyze the adjunctive clinical efficacy of 980‐nm diode laser (DL) irradiation in the treatment of peri‐implant mucositis with mechanical debridement.

Material and methods

Two hundred and twenty patients with one implant diagnosed with peri‐implant mucositis (probing depth [PD] ≥ 4 mm and bleeding on probing [BoP] [primary outcome]) were randomly allocated to test and control treatments. Patients in the control group (n = 110) received debridement using curettes and ultrasonic devices, while patients allocated in the test group (n = 110) received mechanical therapy in combination with DL irradiation (setting 980 nm, 2.5 W, 10 kHz, pw, 30 s). BoP, presence of plaque, and PD were recorded at baseline, 1 month, and 3 months after treatment.

Results

Both therapeutic modalities yielded similar clinical improvements with comparable reductions in the number of BoP‐positive sites, plaque scores, and PD values at 3 months (allp‐values > 0.05). Complete disease resolution was obtained in 38/110 (34.5%) implants in the test group compared with 34/110 (30.9%) implants in the control group at the end of the observation period.

Conclusion

Based on these results, the adjunct use of DL did not yield any statistically significant clinical benefit as compared to nonsurgical mechanical treatment alone in controlling peri‐implant inflammation at 3 months.
Histological, cellular and behavioural analyses of effects of chemotherapeutic agent cyclophosphamide in the developing cerebellum
Authors: Zhang Yu , Li Yongfang , Luo Wenqin , Tang Yaohui , Wang Jia , Yang Ru , Gao Wei‐Qiang
Published: April 2019

Objectives

We performed histological, cellular and behavioural analyses of the effects of cyclophosphamide (CTX), a chemotherapeutic drug, in the developing cerebellum and aimed to provide valuable insights into clinical application of CTX in children.

Materials and methods

C57BL/6 mice and Math1‐dependent GFP expression transgenic mice were used in the research. H&E staining was performed to analyse histological effects of CTX in the cerebellum. Staining for EdU and TUNEL was used to estimate the cell proliferation and apoptosis. Rotarod test and hanging wire test were used to evaluate the behavioural functions. Immunofluorescent staining was used to identify the cell types. The differentiation markers and genes related to Sonic Hedgehog (SHH) signalling were measured via quantitative real‐time PCR or immunoblotting.

Results

We found that while CTX induced a significant reduction in cell proliferation and increased apoptosis in the EGL in 48 hours, the behavioural functions and the multilayer laminar structure of cerebella were largely restored when the mice grew to adults. Mechanistically, granule neuron progenitors, driven by the SHH signalling, enhanced the capability of proliferation quickly after CTX administration was stopped, which allowed the developing cerebellum to catch up and to gradually replenish the injury.

Conclusion

The chemotherapeutic agent CTX induces an immediate damage to the developing cerebellum, but the cerebellar multilayer laminar structure and motor function can be largely restored if the agent is stopped shortly after use.