bluuebunny/crossref_metadata_2025 huggingface dataset:
An individualized risk prediction model for new-onset, progression and regression of chronic kidney disease in a retrospective cohort of patients with type 2 diabetes under primary care in Hong Kong
Authors: Yang Lin , Chu Tsun Kit , Lian Jinxiao , Lo Cheuk Wai , Zhao Shi , He Daihai , Qin Jing , Liang Jun
Published: January 2020

Objectives

This study is aimed to develop and validate a prediction model for multi-state transitions across different stages of chronic kidney disease in patients with type 2 diabetes mellitus under primary care.

Setting

We retrieved the anonymized electronic health records of a population based retrospective cohort in Hong Kong.

Participants

A total of 26,197 patients were included in the analysis.

Primary and secondary outcome measures

The new-onset, progression, and regression of chronic kidney disease were defined by the transitions of four stages that were classified by combining glomerular filtration rate and urine albumin-to-creatinine ratio. We applied a multi-scale multi-state Poisson regression model to estimate the rates of the stage transitions by integrating the baseline demographic characteristics, routine laboratory test results and clinical data from electronic health records.

Results

During the mean follow-up time of 1.7 years, there were 2,935 patients newly diagnosed with chronic kidney disease, 1,443 progressed to the next stage and 1,971 regressed into an earlier stage. The models achieved the best performance in predicting the new-onset and progression with the predictors of sex, age, body mass index, systolic blood pressure, diastolic blood pressure, serum creatinine, HbA1c, total cholesterol, LDL, HDL, triglycerides and drug prescriptions.

Conclusions

This study demonstrated that individual risks of new-onset and progression of chronic kidney disease can be predicted from the routine physical and laboratory test results. The individualized prediction curves developed from this study could potentially be applied to routine clinical practices, to facilitate clinical decision making, risk communications with patients and early interventions.

Article summary

Strengths of this study

Early predictions for chronic kidney disease progression and timely intervention is critical for clinical management of patients with diabetes.

We successfully developed a multi-scale multi-state Poisson regression models that achieved the satisfactory performance in predicting the new-onset and progression of chronic kidney diseases.

The model incorporates the predictors of demographic characteristics, routine laboratory test results and clinical data from electronic health records.

The individualized prediction curves could potentially be applied to facilitate clinical decision making, risk communications with patients and early interventions of CKD progression.

Limitations of this study

The cohort has a relatively short follow-up period and the retrospective study design might suffer from report bias and selection bias.
Structural differences between REM and non-REM dream reports assessed by graph analysis
Authors: Martin Joshua M. , Wainstein Danyal , Mota Natalia B. , Mota-Rolim Sergio A. , Araújo John Fontenele , Solms Mark , Ribeiro Sidarta
Published: January 2020

Dream reports collected after rapid eye movement sleep (REM) awakenings are, on average, longer, more vivid, bizarre, emotional and story-like compared to those collected after non-REM. However, a comparison of the word-to-word structural organization of dream reports is lacking, and traditional measures that distinguish REM and non-REM dreaming may be confounded by report length. This problem is amenable to the analysis of dream reports as non-semantic directed word graphs, which provide a structural assessment of oral reports, while controlling for individual differences in verbosity. Against this background, the present study had two main aims: Firstly, to investigate differences in graph structure between REM and non-REM dream reports, and secondly, to evaluate how non-semantic directed word graph analysis compares to the widely used measure of report length in dream analysis. To do this, we analyzed a set of 125 dream reports obtained from 19 participants in controlled laboratory awakenings from REM and N2 sleep. We found that: (1) graphs from REM sleep possess a larger connectedness compared to those from N2; (2) measures of graph structure can predict ratings of dream complexity, where increases in connectedness and decreases in randomness are observed in relation to increasing dream report complexity; and (3) measures of the Largest Connected Component of a graph can improve a model containing report length in predicting sleep stage and dream complexity. These results indicate that dream reports sampled after REM awakening have on average a larger connectedness compared to those sampled after N2 (i.e. words recur with a longer range), a difference which appears to be related to underlying differences in dream complexity. Altogether, graph analysis represents a promising method for dream research, due to its automated nature and potential to complement report length in dream analysis.
Cortical morphology at birth reflects spatio-temporal patterns of gene expression in the fetal human brain
Authors: Ball G. , Seidlitz J. , O’Muircheartaigh J. , Dimitrova R. , Fenchel D. , Makropoulos A. , Christiaens D. , Schuh A. , Passerat-Palmbach J. , Hutter J. , Cordero-Grande L. , Hughes E. , Price A. , Hajnal J.V. , Rueckert D. , Robinson E.C. , Edwards A.D.
Published: January 2020

Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal MRI in n=292 healthy newborn infants (mean age at birth=39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n=156 samples from 16 brains, aged 12 to 37 post-conceptional weeks). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n=64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations.

Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis of six measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated to estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons; and engaged in stem cell differentiation, neuron migration and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations.

The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.
Cheminformatics Analysis of Natural Product Scaffolds: Comparison of Scaffolds Produced by Animals, Plants, Fungi and Bacteria
Authors: Ertl Peter , Schuhmann Tim
Published: January 2020

Natural products (NPs) have evolved over a very long natural selection process to form optimal interactions with biologically relevant macromolecules. NPs are therefore an extremely useful source of inspiration for the design of new drugs. In the present study we report the results of a cheminformatics analysis of a large database of NP structures focusing on their scaffolds. First, general differences between NP scaffolds and scaffolds from synthetic molecules are discussed, followed by a comparison of the properties of scaffolds produced by different types of organisms. Scaffolds produced by plants are the most complex and those produced by bacteria differ in many structural features from scaffolds produced by other organisms. The results presented here may be used as a guidance in selection of scaffolds for the design of novel NP-like bioactive structures or NP-inspired libraries.
Reliability Assessment of Tissue Classification Algorithms for Multi-Center and Multi-Scanner Data
Authors: Dadar Mahsa , Duchesne Simon ,   For the CCNA Group and the CIMA-Q Group
Published: January 2020

Background

Gray and white matter volume difference and change are important imaging markers of pathology and disease progression in neurology and psychiatry. Such measures are usually estimated from tissue segmentation maps produced by publicly available image processing pipelines. However, the reliability of the produced segmentations when using multi-center and multi-scanner data remains understudied. Here, we assess the robustness of six publicly available tissue classification pipelines across images acquired from different MR scanners and sites.

Methods

We used T1-weighted images of a single individual, scanned in 73 sessions across 27 different sites to assess the robustness of the tissue classification tools. Variability in Dice Kappa values and tissue volumes was assessed for Atropos, BISON, Classify_Clean, FAST, FreeSurfer, and SPM12. We also estimated the sample size necessary to detect a significant 1% volume reduction based on the variability of the estimates from each method within and across scanner models.

Results

BISON had the lowest overall variability in its volumetric estimates, followed by FreeSurfer, and SPM12. All methods also had significant differences between some of their estimates across different scanner manufacturers (e.g. BISON had significantly higher GM estimates and correspondingly lower WM estimates for GE scans compared to Philips and SIEMENs), and different signal-to-noise ratio (SNR) levels (e.g. FAST and FreeSurfer had significantly higher WM volume estimates for high versus medium and low SNR tertiles as well as correspondingly lower GM volume estimates). BISON also had the smallest sample size requirement across all scanners and tissue types, followed by FreeSurfer, and SPM12.

Conclusions

Our comparisons provide a benchmark on the reliability of the publicly used tissue classification techniques and the amount of variability that can be expected when using large multi-center datasets and multi-scanner databases.
Melon ethylene-mediated transcriptome and methylome dynamics provide insights to volatile production
Authors: Feder Ari , Jiao Chen , Galpaz Navot , Vrebalov Julia , Xu Yimin , Portnoy Vitaly , Tzuri Galil , Gonda Itay , Burger Joseph , Gur Amit , Tadmor Yaakov , Schaffer Arthur A. , Lewinsohn Efraim , Katzir Nurit , Fei Zhangjun , Giovannoni James J.
Published: January 2020

During climacteric ripening large-scale transcriptional modifications are governed by ethylene. While ripening-related chromatin modifications are also known to occur, a direct connection between these factors has not been demonstrated. We characterized ethylene-mediated transcriptome modification, genome methylation dynamics, and their relation to organoleptic modifications during fruit ripening in the climacteric melon and an ethylene repressed line where the fruit-specificACC oxidase 1(ACO1) gene was targeted by antisense. TheACO1antisense line exhibited mainly reduced transcriptional repression of ripening-related genes associated with DNA CHH hypomethylation at the onset of ripening. Additionally, transcription of a small set of ethylene-induced genes, including known ripening-associated genes, was inhibited by ACO1 repression and this inhibition was associated with CG hypermethylation. In theACO1antisense line, the accumulation of aromatic compounds, which are mainly derived from the catabolism of amino acids, is known to be inhibited. One of the ethylene-mediated transcriptionally up-regulated genes,CmTHA1, encoding a threonine aldolase, exhibited differential cytosine methylation. Threonine aldolase catalyzes the conversion of L-threonine/L-allo threonine to glycine and acetaldehyde and thus is likely involved in threonine-dependent ethyl ester biosynthesis. Yeast mutant complementation and incubation of melon discs with labeled threonine verified CmTHA1 threonine aldolase activity, revealing an additional ethylene-dependent amino acid catabolism branch involved in climacteric melon ripening.
Cdc42 is required for lymphatic branching, maturation and valve formation during embryonic development
Authors: Jin Yixin , Wang Jian , Liu Yang , Wang Rui , Chen Hailin , Si Hongjiang , Srinivasan Sathish , Tharakan Binu , Zhang Shenyuang L. , Muthuchamy Mariappan , Zawieja David C. , Peng Xu
Published: January 2020

Cdc42, a Ras-related GTPase that regulates the actin cytoskeleton, was recently shown to play an indispensable role in vasculogenesis and endothelial cell (EC) survival. Here, we determined whether Cdc42 also contributes to lymphatic development by generated two different Cdc42 knockout mice lines by crossing Cdc42/flox mice with either vascular endothelial cadherin-Cre (Cdh5α-Cre) mice or Prox1-CreERT2mice. Our results demonstrated that depleting ECs of Cdc42 expression resulted in embryonic lethality with severe edema. Whole-mount immunofluorescence staining of both knockout embryos showed that the deletion of Cdc42 in ECs impaired lymphatic vessel branching and that the lymphatic lumen size significantly increased. Moreover, we found that the inactivation of Cdc42 compromised mesenteric collecting lymphatic vessel maturation and prevented valve formation. We go on to show that Cdc42 can be activated by vascular endothelial growth factor c (VEGFc) in cultured human dermal lymphatic ECs (HDLECs), and that knocking down Cdc42 expression in these cells using siRNA decreased VEGFc-induced focal adhesion kinase (FAK) phosphorylation. These findings, when taken together with the fact that inactivating FAK plus one allele of Cdc42 in ECs was sufficient to recapitulate the phenotypes of the Cdc42 EC knockout embryos, suggests that Cdc42 and FAK interact genetically during lymphatic development. In addition, Cdc42 and FAK regulated signal transduction is essential for blood and lymphatic vessel separation. Taken together, our data highlights the important role played by Cdc42 in the development of the lymphatic system.
Travelling with a parasite: the evolution of resistance and dispersal syndromes during experimental range expansion
Authors: Zilio Giacomo , Nørgaard Louise S. , Gougat-Barbera Claire , Hall Matthew D. , Fronhofer Emanuel A. , Kaltz Oliver
Published: January 2020

Rapid evolutionary change during range expansions can lead to diverging range core and front populations, with the emergence of dispersal syndromes (coupled responses in dispersal and life-history traits). Besides intraspecific effects, range expansions may be impacted by interspecific interactions such as parasitism. Yet, despite the potentially large impact of parasites imposing additional selective pressures on the host, their role on range expansions remains largely unexplored. Using microcosm populations of the ciliateParamecium caudatumand its bacterial parasiteHolospora undulata, we studied experimental range expansions under parasite presence or absence. We found that the interaction of range expansion and parasite treatments affected the evolution of host dispersal syndromes. Namely, front populations showed different associations of population growth parameters and swimming behaviours than core populations, indicating divergent evolution. Parasitism reshaped trait associations, with hosts evolved in the presence of the parasite exhibiting overall increased resistance and reduced dispersal. Nonetheless, when comparing infected range core and front populations, we found a positive association, suggesting joint evolution of resistance and dispersal at the front. We conclude that host-parasite interactions during range expansions can change evolutionary trajectories; this in turn may feed back on the ecological dynamics of the range expansion and parasite epidemics.
Low-temperature crystal structure of the unconventional spin-triplet superconductor UTe2from single-crystal neutron diffraction
Authors: Hutanu Vladimir , Deng Hao , Ran Sheng , Fuhrman Wesley T. , Thoma Henrik , Butch Nicholas P.
Published: January 2020

The crystal structure of a new superconductor UTe2has been investigated using single-crystal neutron diffraction for the first time at the low temperature (LT) of 2.7 K, just above the superconducting transition temperature of ∼1.6 K, in order to clarify whether the orthorhombic structure of typeImmm(No. 71), reported for the room-temperature (RT) structure persists down to the superconducting phase and can be considered as a parent symmetry for the development of spin-triplet superconductivity. In contrast to the previously reported phase transition at about 100 K [Stöwe (1996).J. Solid State Chem.127, 202–210], our high-precision LT neutron diffraction data show that the body-centred RT symmetry is indeed maintained down to 2.7 K. No sign of a structural change from RT down to 2.7 K was observed. The most significant change depending on temperature was observed for the U ion position and the U–U distance along thecdirection, implying its potential importance as a magnetic interaction path. No magnetic order could be deduced from the neutron diffraction data refinement at 2.7 K, consistent with bulk magnetometry. Assuming normal thermal evolution of the lattice parameters, moderately large linear thermal expansion coefficients of about α = 2.8 (7) × 10−5 K−1are estimated.
Pro-active warning system for the crossroads at construction sites based on computer vision
Authors: Zhu Dianchen , Wen Huiying , Deng Yichuan
Published: January 2020

Purpose

To improve insufficient management by artificial management, especially for traffic accidents that occur at crossroads, the purpose of this paper is to develop a pro-active warning system for crossroads at construction sites. Although prior studies have made efforts to develop warning systems for construction sites, most of them paid attention to the construction process, while the accidents that occur at crossroads were probably overlooked.

Design/methodology/approach

By summarizing the main reasons resulting for those accidents occurring at crossroads, a pro-active warning system that could provide six functions for countermeasures was designed. Several approaches relating to computer vision and a prediction algorithm were applied and proposed to realize the setting functions.

Findings

One 12-hour video that films a crossroad at a construction site was selected as the original data. The test results show that all designed functions could operate normally, several predicted dangerous situations could be detected and corresponding proper warnings could be given. To validate the applicability of this system, another 36-hour video data were chosen for a performance test, and the findings indicate that all applied algorithms show a significant fitness of the data.

Originality/value

Computer vision algorithms have been widely used in previous studies to address video data or monitoring information; however, few of them have demonstrated the high applicability of identification and classification of the different participants at construction sites. In addition, none of these studies attempted to use a dynamic prediction algorithm to predict risky events, which could provide significant information for relevant active warnings.
Dyeability and antioxidant activity of artificial silk with Equisetum arvense L. extract
Authors: Park Jiyoung , Park Youngmi
Published: January 2020

Purpose

Equisetum arvense L. (Equisetum) is a weed that is very difficult to remove because of its deep roots. The purpose of this paper is to examine the dyeability and antioxidant activity of Equisetum extracted from hot water.

Design/methodology/approach

Dry Equisetum was extracted at 100°C for 2 h, and its dyeability according to time, temperature and repetition cycle, and the mordant effect by skim milk powder were confirmed. The color change according to the K/S, fastness to rubbing, light, sweat and washing, UV protection rate and antioxidant activity were evaluated.

Findings

UV‒Vis spectroscopy showed that the Equisetum extract contained a flavonoid compound. The addition of Equisetum to artificial silk produced the greatest color difference when dyed at 60°C for 1 h, and the K/S value increased slightly after the pre-mordant treatment. In the fastness test, light and washing had no significant effect, but the fastness to rubbing was very good at Grades 4 and 5, and there was also a considerable improvement in the UV protection rate. The antioxidant activity of the extract was confirmed by an analysis of the radical scavenging ability through the DPPH (1,1-diphenyl 2-picryl-hydrazyl) and ABTS ([2,2’- azino-bis (3-ethylbenzothialzoline-6-sulfonic acid) diammonium salt]) tests.

Originality/value

These results revealed a new natural antioxidant-containing dyestuff, weed grass, which is easy to obtain, easy to use as a dyeing material and has excellent antioxidant activity in an extracted dye solution and dyeing fabric.
An investigation of Confucius Institute’s effects on China’s OFDI via cultural difference and institutional quality
Authors: Xu Chensheng , Yao Feng , Zhang Fan , Wang Yonghong
Published: January 2020

Purpose

This study aims to investigate the influence of the Confucius Institute (CI) on outward foreign direct investment (OFDI) by China and its potential interaction with cultural difference and institutional quality in host countries.

Design/methodology/approach

In the empirical study, the gravity model is adopted as the benchmark to investigate the effects of CI on China's OFDI using the ordinary least squares or Poisson Pseudo Maximum Likelihood estimators. Panel data on China's OFDI from 2004 to 2015 are used. Cultural difference and institutional quality are included explicitly as control variables to examine the effects of CI on China's OFDI.

Findings

CI has a significant positive effect on China’s OFDI, and this effect depends on the cultural difference and institutional quality of the host country. The impact of CI on China’s OFDI is more prominent in host countries with a smaller cultural difference or lower institutional quality.

Originality/value

CI is a comprehensive platform for foreign cultural exchange and signifies the rebirth of Confucianism in China. The present study shows that CI can stimulate the growth of China’s OFDI, with implications for other Asian countries influenced by Confucianism. Based on the results of the study, strategies for “Going Global” and encouraging economic growth based on cultural exchange and the recognition of host country heterogeneities are proposed.
Managing financial and economic risks associated with high-rise apartment building construction in Sri Lanka
Authors: Perera B.A.K.S. , Samarakkody Aravindi Lavanya , Nandasena Shyamani Ruwanthika
Published: January 2020

Purpose

The financial and economic risks associated with high-rise building projects are many. They make project stakeholders to undergo financial difficulties. However, very few past studies have discussed the management of these risks. Thus, the purpose of this paper is to provide a guideline for the effective management of these financial and economic risks associated with high-rise apartment building projects in Sri Lanka.

Design/methodology/approach

The study adopted the mixed research approach. A literature review and semi-structured interviews were used to identify the financial/economic risk factors of high-rise apartment building projects and their risk response measures. The data obtained were used for a questionnaire survey, and the findings were analysed using the mean score method. They were validated using pattern matching. The risk response measures that were identified were ranked according to their effectiveness.

Findings

The findings revealed that “financial problems arising from errors in estimating” is the most significant financial and economic risk factor faced by the property developers involved in high-rise apartment building projects, while “poor contract management” is the most significant financial and economic risk factor faced by the contractors of these projects.

Originality/value

The study recommends a guideline to manage, using effective risk response measures, the financial and economic risk factors that are significant in high-rise apartment building projects.
Education strategy misfit, board effectiveness and Indonesian Islamic bank performance
Authors: Wijayanti Rahma , Diyanty Vera , Laela Sugiyarti Fatma
Published: January 2020

Purpose

This study aims to provide empirical evidence on the contingency factors that affect the implementation of education strategies and the impact of education strategy misfit on the performance and effectiveness of the board’s moderating role on the misfit level and performance of Islamic banks.

Design/methodology/approach

This research is a quantitative study with pooled ordinary least square panel data during the years 2007-2014 from all Indonesian Islamic commercial banks. Islamic bank performances are measured by the level of profitability and sharia financial performance. Board effectiveness is analysed by measuring the effectiveness of both the board of commissioners (BoC) and the sharia supervisory board (SSB).

Findings

This study proves that organisational competent qualities and chief executive officer tenure are the contingency factors that affect the implementation of the education strategy. This study’s results indicate that the effectiveness of both the BoC and SSB has a positive impact on the bank’s profitability and sharia financial performance. The results also show that misfit has a negative effect on sharia financial performance and that board effectiveness is proved to reduce the negative impact of a misfit on sharia financial performance. However, there is no strong evidence that board effectiveness reduces the negative impact of a misfit on profitability.

Originality/value

This study emphasises the importance of enhancing the competence and innovation of organisations in the implementation of education strategy and the need for synergy and increased capabilities among board members to achieve well-established Islamic bank performance.
The Islamic harmonization of consolidated auditors’ reports
Authors: Fakhfakh Mondher
Published: January 2020

Purpose

The purpose of this paper is to examine the level of harmonization of consolidated auditors’ reports issued by the independent auditors of Islamic banks.

Design/methodology/approach

A statistical measurement of the homogenization of the consolidated auditors’ reports of Islamic banks. International and Islamic auditing standards on consolidated auditors’ reports are used as the control (ISA 700 and AAOIFI standard-IAS2).

Findings

The results show a lack of harmonization among the Islamic bank’s groups in several elements related to the form of the consolidated auditor’s report and in all elements related to the independent auditor’s report.

Originality/value

This paper provides new empirical evidence about the measurement of harmonization in the form and content of the consolidated auditors’ reports of Islamic banks groups. It discusses the level of compliance with the consolidated elements enumerated by the standards issued by the International Federation of Accountants and the Accounting and Auditing Organization for Islamic Financial Institutions.
“I know your intention is good, but I still feel bad”
Authors: Shao Bo , Martin Lee
Published: January 2020

Purpose

Drawing on a contagion-interpretation model of leader affective displays and leader effectiveness, the purpose of this paper is to examine the effects of leaders’ angry feedback on followers’ cognitive and affective reactions, and ultimately, perceived leader effectiveness across different cultural contexts.

Design/methodology/approach

In this paper, two experimental studies were conducted with a total of 528 participants.

Findings

The results revealed a culturally divergent cognitive effect: in Western cultures where vertical collectivism is low, leaders’ angry feedback reduced followers’ inferred developmental intention and subsequently, perceived leader effectiveness, whereas in East Asian cultures where vertical collectivism is high, leaders’ angry feedback reduced the two variables to a lesser extent or did not have any effect. In contrast, there was a culturally convergent emotional effect: the impact of leaders’ angry feedback on followers’ negative emotions and subsequently, perceived leader effectiveness was the same, regardless of the level of vertical collectivism.

Originality/value

This research is the first to demonstrate that culture – in particular, the dimension of vertical collectivism – has different impacts on the two mechanisms (i.e. cognitive and affective) through which leader’s angry feedback influences followers’ perceived leader effectiveness.
The Australian Economy in 2019–20: Slower Growth, Record Low Interest Rates and a Changing Housing Landscape
Authors: Tsiaplias Sarantis , Wang Jiao
Published: January 2020

Economic activity in Australia slowed considerably in 2018–19, with domestic demand growth halving and unemployment rising. Consistent with the slowdown, both consumer and wage inflation have remained weak. A synchronised growth slow‐down was observed across major economies, to some extent underpinned by the on‐going US–China trade war. Central banks have responded to weak growth by cutting rates. The US Federal Reserve cut its target for the federal funds rate three times in 2019, as did Australia. To date, record low Australian interest rates have been associated with additional housing‐related debt and asset price appreciation.
The Evolution of EU Antitrust Policy: 1966–2017
Authors: Ibáñez Colomo Pablo , Kalintiri Andriani
Published: January 2020

This article describes, and puts in context, the evolution of the enforcement practice of the European Commission in the area of EU antitrust law (Articles 101 and 102 TFEU). It considers all formal decisions adopted in the period between 1966 – when the European Court of Justice delivered the two seminal rulings that marked the discipline – and the end of 2017. The article classifies Commission decisions in accordance with four enforcement paradigms. The descriptive statistics show that the cases that the Commission chooses to prioritise have changed over the years. First, enforcement has progressively moved towards the core and the outer boundaries of the system. Second, it has become policy‐driven rather than law‐driven. Third, the nature of the cases chosen by the Commission is consistent with its commitment to a ‘more economics‐based approach’ to enforcement. Finally, these cases signal a move towards a more ambitious stage in the process of the integration of Member States’ economies.
Enhancing the sweetening power of lactose by enzymatic modification in the reformulation of dairy products
Authors: Luzzi Giuseppina , Steffens Marco , Clawin‐Rädecker Ingrid , Hoffmann Wolfgang , Franz Charles M A P , Fritsche Jan , Lorenzen Peter Chr
Published: January 2020

Lactose solutions of up to 50% (w/v) were incubated with lactases and glucose isomerases for subsequent implementation in dairy product samples to enhance sweetness. A degree of hydrolysis of >90% and of isomerisation of 50% were attainable. The sensory sweetening power of lactose in solutions of up to 50% (w/v) can be enhanced 2–3 times. Based on sensory experiments, application of this bi‐enzymatic system in yoghurt and pudding samples allowed for a 10–20% (w/w) reduction in the total sugar content, whilst retaining equal sweetness. The growth of yoghurt starter cultures was not affected, yet furosine formation more than doubled in high heated, enzyme‐modified milk.
Topical application of ketamine to prevent postoperative sore throat in adults: A systematic review and meta‐analysis
Authors: Kuriyama Akira , Nakanishi Misuzu , Kamei Jun , Sun Rao , Ninomiya Kohei , Hino Masaaki
Published: January 2020

Background

Postoperative sore throat is a leading undesirable postoperative outcome. Ketamine is an N‐methyl‐d‐aspartate receptor antagonist and its topical application is used for chronic pain and oral/throat indications. We conducted a systematic review to assess the efficacy of preoperative, topical ketamine application for preventing postoperative sore throat.

Methods

We searched MEDLINE, EMBASE, and CENTRAL through September 23, 2019 for randomized controlled trials in which at least one intervention was topical ketamine to prevent postoperative sore throat in adults undergoing endotracheal intubation. The primary outcome was the incidence of sore throat at 24 hours postoperatively. The comparators were non‐analgesic controls (placebo, no treatment, or usual care) or active agents. We pooled the data using a random‐effects model.

Results

We included 41 randomized controlled trials involving 3784 participants. Topical ketamine was associated with reduced incidence of sore throat at 24 hours postoperatively compared to non‐analgesic methods (risk ratio, 0.45; 95% CI, 0.37‐0.54;P < .001). We found significant publication bias, but the results remained unchanged with a trim‐and‐fill analysis. Trial sequential analysis (TSA) suggested that the efficacy of topical ketamine was adequate (TSA‐adjusted 95% CI, 0.33‐0.56). The GRADE quality for this evidence was moderate. Topical ketamine was inferior to a combination of nebulized ketamine and clonidine in preventing postoperative sore throat.

Conclusions

Preoperative, topical ketamine application may be more effective than non‐analgesic methods in preventing postoperative sore throat. The number of studies did not suffice to determine the place of topical ketamine among agents to prevent postoperative sore throat.
Nicotine delivery and users’ reactions to Juul compared with cigarettes and other e‐cigarette products
Authors: Hajek Peter , Pittaccio Kate , Pesola Francesca , Myers Smith Katie , Phillips‐Waller Anna , Przulj Dunja
Published: January 2020

Aims

To assess the pharmacokinetic (PK) profile of, and users’ reactions to, Juul (59 mg nicotine/ml) as an indication of its therapeutic and dependence potential.

Design

Cross‐over, within‐subjects study in which participants attended after overnight abstinence on separate sessions and smoked a cigarette or used Juul or eight other types of e‐cigarettes (EC)ad libitumfor 5 minutes. The Juul product used was the version available in the United States that has more nicotine in the e‐liquid than the one available in the European Union.

Setting

Laboratory setting in the United Kingdom.

Participants

Twenty dual users (smokers who also vape) provided data on Juul and cigarettes, with eight also providing data on other EC products.

Measurements

At each session, number of puffs taken was counted during the 5‐minute product use period and blood samples were taken at baseline and at 2, 4, 6, 8, 10 and 30 minutes after starting smoking/vaping and analysed for nicotine. Participants also monitored their urges to smoke and rated the products on a range of characteristics.

Findings

Juul's PK profile was close to the PK profile of cigarettes [maximum concentration (Cmax) = 20.4 versus 19.2 ng/ml; time to maximum concentration (Tmax) = 4 versus 6 minutes; area under the curve (AUC): 307.9 versus 312.6, respectively]. Compared with other EC products, Juul had shorter Tmax[4 minutes, (IQR = 2.5–4.0) versus 6.3 minutes, (IQR = 4.7 – 8.1),P= 0.012] and higher Cmax(28.9 (SD = 15.6) versus 10.6 (SD = 5.5),P= 0.013) despite a lower number of puffs (12.5 (SD = 4.2) versus 17.0 (SD = 4.2),P= 0.084). Compared with other e‐cigarette products, it also provided faster reduction of urges to smoke and obtained more favourable subjective ratings.

Conclusion

Juul's PK profile and user ratings suggest that it could be more effective than other EC products in helping smokers to quit smoking, but it may also have a higher potential to generate regular use in non‐smokers.
Corrosion casting of the cardiovascular structure in adult zebrafish for analysis by scanning electron microscopy and X‐ray microtomography
Authors: De Spiegelaere Ward , Caboor Lisa , Van Impe Matthias , Boone Matthieu N. , De Backer Julie , Segers Patrick , Sips Patrick
Published: January 2020

Zebrafish have come to the forefront as a flexible, relevant animal model to study human disease, including cardiovascular disorders. Zebrafish are optically transparent during early developmental stages, enabling unparalleled imaging modalities to examine cardiovascular structure and function in vivo and ex vivo. At later stages, however, the options for systematic cardiovascular phenotyping are more limited. To visualise the complete vascular tree of adult zebrafish, we have optimised a vascular corrosion casting method. We present several improvements to the technique leading to increased reproducibility and accuracy. We designed a customised support system and used a combination of the commercially available Mercox II methyl methacrylate with the Batson's catalyst for optimal vascular corrosion casting of zebrafish. We also highlight different imaging approaches, with a focus on scanning electron microscopy (SEM) and X‐ray microtomography (micro‐CT) to obtain highly detailed, faithful three‐dimensional reconstructed images of the zebrafish cardiovascular structure. This procedure can be of great value to a wide range of research lines related to cardiovascular biology in small specimens.
Allergen alters IL‐2/αIL‐2‐based Treg expansion but not tolerance induction in an allergen‐specific mouse model
Authors: Köhler Cordula , Smole Ursula , Kratzer Bernhard , Trapin Doris , Schmetterer Klaus G. , Pickl Winfried F.
Published: January 2020

Background

Regulatory T lymphocytes (Treg) play an important role in preventing allergic diseases. We characterized Treg expansion kinetics, marker profiles, and recirculation behavior in allergen‐challenged mice, which had been pretreated with IL‐2/αIL‐2 complexes in the presence or absence of allergen. Moreover, the ability of induced Treg to control airway hyperreactivity and effector functions of lung T cells was determined.

Methods

Humanized TCR/HLA‐transgenic allergy mice were treated in vivo with recombinant IL‐2 complexed to the anti‐IL‐2 mAb JES6‐1 in the presence or absence of mugwort pollen extract (MPE) on days 0‐2. Afterward, they were intranasally challenged with MPE (days 13‐15) followed by determination of airway hyperreactivity and lung T cell effector functions. Multiparametric flow cytometry on peripheral blood T cells was performed on a daily basis.

Results

IL‐2/αIL‐2 complexes highly efficiently expanded peripheral Treg cells, while concomitant allergen exposure altered the phenotype of expanded Treg cells. Notably, application of allergen together with IL‐2/αIL‐2 complexes induced expression of Treg marker molecules CTLA4, NRP1, Helios, and GITR on conventional T cells. Apart from CD25, GARP was identified as the most reliable surface‐expressed lineage discrimination marker of Treg expanded in the presence of IL‐2/αIL‐2 complexes and allergen. Finally, IL‐2/αIL‐2 complex‐expanded Treg cells could be recalled upon allergen challenge, which was associated with suppression of lung‐specific Th2 responses long after initial treatment.

Conclusion

The characterization of reliable surface and transcription markers of IL‐2/αIL‐2 complex‐expanded Treg along with their expansion kinetics and function will help to identify protocols for their long‐term expansion in vivo.
Accuracy of high‐resolution ultrasonography in establishing the diagnosis of carpal tunnel syndrome
Authors: Aggarwal Purnima , Jirankali Vivek , Garg Sudhir K.
Published: January 2020

Background

The aim of this study was to evaluate the accuracy of high‐resolution ultrasonography in the diagnosis of carpal tunnel syndrome (CTS).

Methods

It included 50 patients with signs and symptoms suggestive of CTS and 50 individuals as control group. Cross‐sectional area of median nerve at the inlet of carpal tunnel was measured in control as well as symptomatic group by ultrasonography. In addition, nerve conduction studies (NCS) were carried out in the symptomatic group. Radiologists performing the ultrasonography were blinded to the results of NCS. Sensitivity, specificity and accuracy of ultrasonography and NCS in the diagnosis of CTS were calculated and compared.

Results

In control group, cross‐sectional area of the median nerve ranged between 5 and 7.3 mm2, whereas in the symptomatic group it varied from 8.4 to 16.5 mm2. It was >9 mm2 in 47 patients. With a cut‐off of 9 mm2, sensitivity, specificity and accuracy of ultrasonography in diagnosing CTS were 95%, 100% and 97%, respectively. NCS was diagnostic of CTS in 48 (96%) patients.

Conclusion

Ultrasonographic examination gives similar results to NCS in establishing diagnosis of CTS and can be used as a screening modality with further use of NCS in cases where ultrasonography is non‐diagnostic.
A Bayesian multi‐risks survival (MRS) model in the presence of double censorings
Authors: de Castro Mário , Chen Ming‐Hui , Zhang Yuanye , D'Amico Anthony V.
Published: January 2020

Semi‐competing risks data include the time to a nonterminating event and the time to a terminating event, while competing risks data include the time to more than one terminating event. Our work is motivated by a prostate cancer study, which has one nonterminating event and two terminating events with both semi‐competing risks and competing risks present as well as two censoring times. In this paper, we propose a new multi‐risks survival (MRS) model for this type of data. In addition, the proposed MRS model can accommodate noninformative right‐censoring times for nonterminating and terminating events. Properties of the proposed MRS model are examined in detail. Theoretical and empirical results show that the estimates of the cumulative incidence function for a nonterminating event may be biased if the information on a terminating event is ignored. A Markov chain Monte Carlo sampling algorithm is also developed. Our methodology is further assessed using simulations and also an analysis of the real data from a prostate cancer study. As a result, a prostate‐specific antigen velocity greater than 2.0 ng/mL per year and higher biopsy Gleason scores are positively associated with a shorter time to death due to prostate cancer.
Semiparametric modelling and estimation of covariate‐adjusted dependence between bivariate recurrent events
Authors: Ning Jing , Cai Chunyan , Chen Yong , Huang Xuelin , Wang Mei‐Cheng
Published: January 2020

A time‐dependent measure, termed the rate ratio, was proposed to assess the local dependence between two types of recurrent event processes in one‐sample settings. However, the one‐sample work does not consider modeling the dependence by covariates such as subject characteristics and treatments received. The focus of this paper is to understand how and in what magnitude the covariates influence the dependence strength for bivariate recurrent events. We propose the covariate‐adjusted rate ratio, a measure of covariate‐adjusted dependence. We propose a semiparametric regression model for jointly modeling the frequency and dependence of bivariate recurrent events: the first level is a proportional rates model for the marginal rates and the second level is a proportional rate ratio model for the dependence structure. We develop a pseudo‐partial likelihood to estimate the parameters in the proportional rate ratio model. We establish the asymptotic properties of the estimators and evaluate the finite sample performance via simulation studies. We illustrate the proposed models and methods using a soft tissue sarcoma study that examines the effects of initial treatments on the marginal frequencies of local/distant sarcoma recurrence and the dependence structure between the two types of cancer recurrence.
Can sensory integration have a role in multi‐element behavioural intervention? An evaluation of factors associated with the management of challenging behaviour in community adult learning disability services
Authors: Mc Gill Ciara , Breen Cathal J.
Published: January 2020

Accessible summary

Sensory integration is about how our brain receives and processes information so we can make sense of our everyday life.

Behavioural interventions is a term used to describe how to teach people to increase useful behaviours or decrease behaviours that are challenging.

Some people with severe learning disabilities can have behaviour that challenges and this can be difficult to manage.

To manage behaviours that challenge restrictive interventions have been used such as people being given medication, or being held by others against their will.

Instead of using these restrictive interventions we can use sensory strategies and a low stimulus environment which have been found to be successful in managing behaviours that challenge.

Introduction

Adults with complex needs and severe learning disability present as a serious management problem within the community. Restrictive interventions are often used to manage adults with these issues, even though best practice recommends the use of positive behaviour support. Positive behaviour support involves functional analysis, but it does not specifically focus on sensory integration difficulties as a contributing factor to challenging behaviour.

Methods

A systematic search of the literature was completed using a range of electronic databases, an electronic search, hand search and review of reference lists. Seven relevant studies were identified. These studies were critically appraised and analysed. However, the extent of research was limited and the procedural quality variable, some distinct themes, arose.

Results

Out of the seven intervention studies included in this review, two studies used sensory integration therapy, three employed multi‐element behavioural intervention, one utilised environmental stimulation within a multifactor behavioural intervention approach and one used sensory strategies within a structured behavioural intervention programme. The participants across the final seven papers reviewed consisted mainly of males with a high incidence of participants presenting with ASD. A range of assessment tools and outcome measures were used.

Conclusions

The use of restrictive intervention is still an issue in practice. Nearly all the studies reviewed stressed the issue of placing individuals with severe challenging behaviour in the community. Behavioural studies have successfully utilised sensory integration strategies within a structured behavioural format to manage challenging behaviour in a community setting for adults with a learning disability.
Cutaneous metastasis of SMARCA4‐deficient thoracic sarcoma: A diagnostic dilemma with therapeutic implications
Authors: Leckey Bruce D. , Selim M. Angelica , Al‐Rohil Rami N.
Published: January 2020

SMARCA4‐deficient thoracic sarcoma (SMARCA4‐DTS) is a recently recognized entity with undifferentiated rhabdoid morphology and mutations in the switch/sucrose nonfermenting BRG1‐associated factors complex. Patients are typically males in their fifth decade with a history of smoking who present with rapidly progressive intrathoracic disease and follow an aggressive clinical course. Metastatic disease is reported in up to 77% of cases; however, to our knowledge, cutaneous metastasis has not been reported nor has it been reported as the initial manifestation of the disease. Recognizing SMARCA4‐DTS from other types of epithelioid tumors that involve the skin is clinically relevant, as targeted therapies for SMARC‐deficient tumors are currently being investigated and early clinical trial data show therapeutic benefit.