bluuebunny/crossref_metadata_2025 huggingface dataset:
The scope of exclusionary public response to the European refugee crisis
Authors: NORDØ ÅSTA DYRNES , IVARSFLATEN ELISABETH
Published: June 2021

We know from previous research that an exclusionary reaction in public opinion is likely following a sudden and large‐scale influx of refugees of the sort experienced in many European countries in 2015. Yet, we know much less about the scope of these expected reactions. This article makes a conceptual and empirical contribution to the analysis of the scope of exclusionary reactions following a refugee crisis. Conceptually, we distinguish between three scope dimensions: substantive reach, duration and politicization. Empirically, we evaluate each of the scope dimensions using seven‐wave panel‐data collected before, during and after the large‐scale influx of refugees to Norway. We find that the expected exclusionary reaction (a) spilled over to opinion about immigration broadly speaking; (b) endured in that it lasted long after the situation in Norway had been brought under control; (c) encompassed voters of all political stripes. Nevertheless, we also document an important limitation to the scope of the reaction: The sudden influx of refugees to Norway did not cause a permanent shift in public opinion. Approximately two years after the situation had been brought under control, opinion about both refugee rights and immigration generally had reverted back to pre‐crisis baseline levels. Interestingly, the conceptual and empirical analysis suggests that public opinion dynamics following a sudden and large‐scale influx of refugees is similar to that found in response to other forms of large national or international crises.
Back to Amido Black: Uncovering touch DNA in blood‐contaminated fingermarks
Authors: Harush‐Brosh Yinon , Levy‐Herman Yael , Bengiat Ravell , Oz Carla , Levin‐Elad Michal , Horowitz Michal , Faerman Marina
Published: June 2021

Blood‐contaminated fingermarks (FMs) found in violent crime scenes may directly connect the suspect to the crime by linking the FM to the suspect and the DNA from the blood to the victim. However, marks that are incomparable are considered “dead‐evidence” as the link to the suspect is lost. In this study, a novel approach was attempted to uncover the trace amount of touch DNA of the suspect in such marks. We examined the effect of two enhancement methods, ninhydrin (NIN) and amido black (AB), on DNA recovery from blood‐contaminated FMs. A total of 108 fingerprints were deposited in three sets of depleted blood prints, blood‐contaminated FMs, and latent FMs. All FMs were developed by either NIN or AB, or left undeveloped as reference followed by the quantification of the total DNA amount. This work shows that while AB had a detrimental effect on the quantity of blood‐derived DNA specifically, reducing it by half, no similar effect was observed for touch DNA in latent FMs. This reduction led to the alteration of the major‐to‐minor DNA profile ratio to 70:30, thus enabling to obtain two distinct DNA profiles of the suspect from the touch DNA as well as the victim's profile from the blood. From an operational perspective, the use of AB in crime scenes may have an added value to retrieve the crucial DNA profile of the suspect, thus resurrecting a “dead‐evidence.”
A comparison of Janus kinase inhibitor safety in rheumatoid arthritis
Authors: Nash Peter , Lim Irwin , Marabani Mona
Published: June 2021

The last decade has seen considerable advancement in the treatment options available to patients with rheumatoid arthritis (RA) through the development of oral, small molecules that target and inhibit Janus kinases (JAKi). These drugs have a rapid onset of action, disrupting the Janus kinase/signal transducer and activator of transcription pathway and preventing the production of cytokines involved in inflammatory processes. They have the potential to provide immunomodulatory benefits across a broad range of diseases. This narrative review focuses on the safety profile of tofacitinib, baricitinib, upadacitinib, and filgotinib. Although JAKi have been shown to be effective in the treatment of RA, it is posited that they have different selectivities, which are likely to affect their safety profiles in RA patients. Currently, there are limited long‐term safety data available, with most data coming from randomized controlled trials. However, the data that are available show that upadacitinib and filgotinib may have improved safety profiles. This is particularly true in relation to herpes zoster, venous thromboembolism, and gastrointestinal perforation. Future research is needed to investigate the safety and efficacy of switching between JAKi when a previous JAKi has not been tolerated or has been ineffective.
‘Powerful knowledge’, ‘cultural literacy’ and the study of literature in schools
Authors: Eaglestone Robert
Published: June 2021

There is no doubting the influence of E.D. Hirsch and Michael Young on UK education policy and practice over the last ten years. Hirsch’s notion of ‘cultural literacy’ and Young’s idea of ‘powerful knowledge’ are the theoretical drivers of a national shift towards ‘knowledge‐led’ or ‘knowledge‐rich’ school curricula. Evidence of this shift is plain to see in the current iteration of the National Curriculum for England and in the mission statements of a growing number of schools and academy trusts across the country.

According to Robert Eaglestone, however, there is a mistake under the floorboards of the new, knowledge‐rich curriculum. It is a mistake that damages and distorts teaching in a number of curriculum subjects, but Eaglestone ‐ a literary critic and theorist ‐ focuses on its disastrous impact on the teaching of literature. Both Hirsch and Young fall prey to scientism: they take knowledge in the natural sciences as a template for knowledge across the board. Eaglestone shows first how scientism is baked into the theories of ‘cultural literacy’ and ‘powerful knowledge’, then how the adoption of these theories in schools has disfigured and diminished the teaching of literature.

Eaglestone’s argument is arresting, timely and compelling. For those tasked with planning and teaching English curricula in schools, his penetrating analysis of where things have gone wrong and how to put them right will be revelatory and transformative. And for those concerned with curriculum theory and education policy more generally, it will reinvigorate and reorient the debate about what is helpful and what is not in the work of E.D. Hirsch and Michael Young.
Enhanced NRF2 expression mitigates the decline in neural stem cell function during aging
Authors: Anandhan Annadurai , Kirwan Konner R. , Corenblum Mandi J. , Madhavan Lalitha
Published: June 2021

Although it is known that aging affects neural stem progenitor cell (NSPC) biology in fundamental ways, the underlying dynamics of this process are not fully understood. Our previous work identified a specific critical period (CP) of decline in NSPC activity and function during middle age (13–15 months), and revealed the reduced expression of the redox‐sensitive transcription factor, NRF2, as a key mediator of this process. Here, we investigated whether augmenting NRF2 expression could potentially mitigate the NSPC decline across the identified CP. NRF2 expression in subventricular zone (SVZ) NSPCs was upregulated via GFP tagged recombinant adeno‐associated viral vectors (AAV‐NRF2‐eGFP), and its cellular and behavioral effects compared to animals that received control vectors (AAV‐eGFP). The vectors were administered into the SVZs of aging rats, at time points either before or after the CP. Results indicate that animals that had received AAV‐NRF2‐eGFP, prior to the CP (11 months of age), exhibited substantially improved behavioral function (fine olfactory discrimination and motor tasks) in comparison to those receiving control viruses. Further analysis revealed that NSPC proliferation, self‐renewal, neurogenesis, and migration to the olfactory bulb had significantly increased upon NRF2 upregulation. On the other hand, increasing NRF2 after the CP (at 20 months of age) produced no notable changes in NSPC activity at either cellular or behavioral levels. These results, for the first time, indicate NRF2 pathway modulation as a means to support NSPC function with age and highlight a critical time‐dependency for activating NRF2 to enhance NSPC function.
Considerations regarding species distribution models for forest insects
Authors: Koch Frank H.
Published: June 2021

Species distribution models, or SDMs, have become important decision support tools by answering fundamental questions about where species, including invasive species, are likely to survive and thrive based on environmental conditions.

For an inexperienced modeller or model reviewer, the terminology and technical aspects of SDMs can be overwhelming, and even well‐trained modellers can struggle to understand the implications of various modelling choices.

Here, I outline some key considerations with respect to SDMs, focusing on their application to forest insects. Foremost, I assert that a model should be developed and evaluated with attention to relationships between an insect and its hosts, as those relationships determine much about the places the insect may occupy.

In my view, the most successful models are constructed carefully and incorporate honest assessments of their limitations, sources of error and uncertainty, and the degree of linkage between the model and the real‐world circumstances it is meant to portray.
Redemption through Rebellion: Border Change, Lost Unity, and Nationalist Conflict
Authors: Cederman Lars‐Erik , Rüegger Seraina , Schvitz Guy
Published: June 2021

Are past border changes responsible for today's civil wars? Departing from conventional, state‐centric research designs, this article examines this question by focusing on “aggregate” ethnic groups, which are defined independently of state borders. Introducing a new index of “territorial fractionalization” that measures how fragmented such groups are across states, we postulate that higher fragmentation is linked to a greater risk of civil conflict. Furthermore, we expect that groups that experienced increases in fragmentation are particularly violence prone, as illustrated by postimperial revisionism and other cases of irredentism and secession. To test our arguments, we combine geocoded data on ethnic settlement areas with our own newly collected data on international borders since 1886, complemented by mediation analysis based on ethnonationalist claims. Covering ethnic groups around the world since 1946 through 2017, our findings are robust to the inclusion of control variables, fixed effects, and the use of alternative historical ethnicity data sets.
Comparative efficacy and safety of preserved versus preservative‐free beta‐blockers in patients with glaucoma or ocular hypertension: a systematic review
Authors: Skov Anne Guldhammer , Rives Amalie Santaolalla , Freiberg Josefine , Virgili Gianni , Azuara‐Blanco Augusto , Kolko Miriam
Published: June 2021

Preservative‐free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta‐analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta‐blockers, or combination using beta‐blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow‐up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow‐up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative‐free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07–0.51 mmHg, p = 0.010; moderate‐certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break‐up time (TBUT) was better with preservative‐free drops (p < 0.001). Schirmer’s test was better in the preservative‐free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative‐free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative‐free medications, more evidence is needed. The increasing use of preservative‐free drops may be associated with better ocular surface and tolerability, but strong evidence from RCTs would be welcome.
Effective, but not all the time: Experimental evidence on the effectiveness of a code of ethics' design
Authors: Kotzian Peter , Stöber Thomas , Weißenberger Barbara E. , Hoos Florian
Published: June 2021

Relations between society and business are increasingly characterized by the societal demand for compliance with ethical standards. Companies are held responsible for behavior of their employees, which increases the demand for effective internal governance. To assure compliance, many companies enact codes of ethics. Despite a common core of ethical standards, codes differ considerably in formal design elements. Albeit theory suggests that a code's formal design, that is, how a code's content is presented, affects its behavioral impact, there is little research on this issue. Addressing this research gap, we conducted a between‐subjects experiment (factorial survey) in which we manipulated design elements of codes and examined how these elements affect behavioral intentions in various business situations. Holding the code's content constant, we manipulated its tone (positive vs. negative) and whether it was signed by the company's executive board (with vs. without signature). Our results indicate that the effectiveness of a code can be improved by using signed codes, while there is no effect for a code's tone. Our paper contributes designing internal governance in two ways: by giving experimental evidence on the relevance of a code's formal design and by providing practical guidance how to increase code effectiveness.
Renin–angiotensin system in intestinal inflammation—Angiotensin inhibitors to treat inflammatory bowel diseases?
Authors: Salmenkari Hanne , Korpela Riitta , Vapaatalo Heikki
Published: June 2021

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin–angiotensin system (RAS), besides being antihypertensive, also possess anti‐inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.
Development and preliminary validation of the patient-reported Chronic Itch Burden Scale assessing health-related quality of life in chronic pruritus
Authors: Theunis J. , Nordon C. , Falissard B. , Orri M. , Mengeaud V. , Misery L.
Published: June 2021

Background

Chronic pruritus (CP) significantly affects patients’ health-related quality of life (HRQoL). Very few self-reported HRQoL questionnaires exploring CP have been developed according to international guidelines, thus limiting their use in preauthorization trials.

Objectives

To develop a self-reported HRQoL questionnaire in patients with CP owing to psoriasis, atopic dermatitis, seborrhoeic dermatitis of the scalp or idiopathic dermatitis, and to explore the preliminary psychometric properties of the questionnaire.

Methods

The study was performed in France. A conceptual framework was developed based on a structured literature review and expert insight, and was improved using three focus groups involving 19 participants. A 50-item questionnaire was created and tested with 21 participants using cognitive debriefings; 11 items were removed. A cross-sectional study including 251 participants was performed to explore the preliminary psychometric properties of the 39-item questionnaire. Dimensionality was explored using principal component analysis. Cronbach’s alpha and correlation coefficients (interitem, item-total score and item-dimension score) were measured. The number of items was reduced through expert consensus.

Results

In the 39-item version, three main dimensions were identified (Cronbach’s alpha = 0·94) and all correlation coefficients were > 0·34. Upon review, 13 items were deleted owing to poor quality and six items were deleted by the team, generating a 20-item version. The questionnaire’s factorial structure was best reflected with a two-dimension solution, i.e. (i) social and emotional repercussions and (ii) relation to others, fear of judgement.

Conclusions

The Chronic Itch Burden Scale patient-reported questionnaire explores broad aspects of HRQoL that are relevant for patients with various skin diseases. Its good cross-sectional validity makes it useful for trials and practitioners.
ICT self‐efficacy mediates most effects of university ICT support on preservice teachers' TPACK: Evidence from three normal universities in China
Authors: Wang Qiong , Zhao Guoqing
Published: June 2021

A thorough understanding of how ICT support provided by teacher preparation programmes influences preservice teachers' technological pedagogical content knowledge (TPACK) has become increasingly essential. This study aimed at exploring the mediating role of ICT perception, perceived ICT competence and ICT self‐efficacy between university ICT support and preservice teachers' TPACK. Data were collected through an online self‐assessment questionnaire translated and adapted from existing studies and verified with confirmatory factor analysis (CFA). A total of 298 preservice teachers, who were senior students studying at three different normal universities in China, participated in this study. Structural equation modelling revealed the following: (a) university ICT support significantly predicted preservice teachers' ICT perception, perceived ICT competence and ICT self‐efficacy, but had no significant direct effects on their TPACK; (b) ICT self‐efficacy was a strong predictor of preservice teachers' TPACK and ICT perception was a weak one, while perceived ICT competence did not predict TPACK at all; and (c) among three potential mediators, ICT self‐efficacy mediated the most effects of university ICT support on preservice teachers' TPACK. These findings demonstrate strong positive effects of institutional support on preservice teachers' TPACK development, which was strongly underestimated in previous studies. Findings suggest normal universities should create practical opportunities for preservice teachers to perceive the power of technology, especially opportunities that could improve preservice teachers' self‐efficacy while applying technology into instruction.

Practitioner notes

What is already known about this topic

ICT support from schools is an essential precondition while enhancing in‐service teachers' motivation to apply ICT into instruction.

Research revealing how ICT support provided by teacher preparation programmes affects preservice teachers' TPACK is absent.

What the paper adds

This study adds to the previous literature by exploring the mediating role of ICT perception, perceived ICT competence and ICT self‐efficacy in the relationship between university ICT support and preservice teachers' TPACK.

This study found that university ICT support significantly predicted preservice teachers' ICT perception, perceived ICT competence and ICT self‐efficacy, but had no significant direct effects on their TPACK.

Among the three potential mediators, ICT self‐efficacy mediated the most effects of university ICT support on preservice teachers' TPACK.

Implications for practice and/or policy

Normal universities need to provide effective and professionally targeted ICT support to meet preservice teachers' needs.

The mediating role of ICT self‐efficacy should be highlighted on the path from university ICT support to TPACK.
Insights into the mechanisms underlying opioid use disorder and potential treatment strategies
Authors: Cao Dan‐Ni , Li Fei , Wu Ning , Li Jin
Published: June 2021

Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non‐opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development.

LINKED ARTICLES

This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Why aren't warning signals everywhere? On the prevalence of aposematism and mimicry in communities
Authors: Kikuchi David W. , Herberstein Marie E. , Barfield Michael , Holt Robert D. , Mappes Johanna
Published: June 2021

Warning signals are a striking example of natural selection present in almost every ecological community – from Nordic meadows to tropical rainforests, defended prey species and their mimics ward off potential predators before they attack. Yet despite the wide distribution of warning signals, they are relatively scarce as a proportion of the total prey available, and more so in some biomes than others. Classically, warning signals are thought to be governed by positive density‐dependent selection, i.e. they succeed better when they are more common. Therefore, after surmounting this initial barrier to their evolution, it is puzzling that they remain uncommon on the scale of the community. Here, we explore factors likely to determine the prevalence of warning signals in prey assemblages. These factors include the nature of prey defences and any constraints upon them, the behavioural interactions of predators with different prey defences, the numerical responses of predators governed by movement and reproduction, the diversity and abundance of undefended alternative prey and Batesian mimics in the community, and variability in other ecological circumstances. We also discuss the macroevolution of warning signals. Our review finds that we have a basic understanding of how many species in some taxonomic groups have warning signals, but very little information on the interrelationships among population abundances across prey communities, the diversity of signal phenotypes, and prey defences. We also have detailed knowledge of how a few generalist predator species forage in artificial laboratory environments, but we know much less about how predators forage in complex natural communities with variable prey defences. We describe how empirical work to address each of these knowledge gaps can test specific hypotheses for why warning signals exhibit their particular patterns of distribution. This will help us to understand how behavioural interactions shape ecological communities.
Nonchalant neighbors: Space use and overlap of the critically endangered Elongated Tortoise
Authors: Ward Matthew , Marshall Benjamin Michael , Hodges Cameron Wesley , Montano Ysabella , Artchawakom Taksin , Waengsothorn Surachit , Strine Colin Thomas
Published: June 2021

To prevent population extirpations, we need to understand a species’ requirements, especially for critically endangered species inhabiting biodiversity hotspots. Studying animal movement provides necessary insights and gauges protected area effectiveness. Southeast Asian protected areas are becoming isolated, stressing the need for maintaining population viability. We used radio‐telemetry with the critically endangered Elongated Tortoise (Indotestudo elongata) to assess: movements, space use, and conspecific overlap in a small protected area—Sakaerat Biosphere Reserve, Thailand. Movements were weakly seasonal, higher in hot and wet seasons than the dry season, and annual space use varied (4.24–55.57 ha), with conspecifics frequently overlapping. Conspecific comparisons revealed males (n = 5) moved similarly to females (n = 12) but used larger areas. Despite more instances of conspecific attraction over avoidance (20:8), avoidance/attraction behavior appeared disconnected from individual size; therefore, interaction patterns may result from resources locations (mates or food) rather than competition (i.e., no evidence of smaller individuals avoiding larger individuals). Female–female attraction suggests no resource exclusion tactics at our temporal resolution. Male–female attraction may indicate seasonal reproductive movements, but we could not detect significant interactive effects linking conspecific attraction or step length to breeding activity. Our observations of annual space use and overlap present critical components when designing robust population assessments underlining any successfulI.elongataconservation effort. In the context of previous work connecting space overlap with population viability, our results suggest the biosphere population ofI.elongatato be reproductive, with enough resources to be viable, emphasizing the importance of relatively small protected natural areas.
ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta‐analysis
Authors: Karimi Leila , Vijverberg Susanne J. , Engelkes Marjolein , Hernandez‐Pacheco Natalia , Farzan Niloufar , Soares Patricia , Pino‐Yanes Maria , Jorgensen Andrea L. , Eng Celeste , Mukhopadhyay Somnath , Schieck Maximilian , Kabesch Michael , Burchard Esteban G. , Chew Fook Tim , Sio Yang Yie , Potočnik Uroš , Gorenjak Mario , Hawcutt Daniel B. , Palmer Colin N. , Turner Steve , Janssens Hettie M. , Maitland‐van der Zee Anke H. , Verhamme Katia M. C. ,   the PiCA and SysPharmPedia consortia
Published: June 2021

Background

The polymorphism Arg16 in β2‐adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long‐acting β2‐agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27.

Objective

We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA.

Methods

The study was undertaken using data from 10 independent studies (n = 5903) participating in the multi‐ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma‐related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta‐analysed using the inverse variance weighting method assuming random‐effects.

Results

In subjects treated with ICS and LABA (n = 832, age: 3–21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05–1.87, I2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05–1.94, I2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71–1.39, I2 = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as‐required short‐acting β2‐agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686).

Conclusion and clinical relevance

The ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype‐guided treatment which might improve clinical outcomes in asthmatic patients.
A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects
Authors: Erol Seyit Ahmet , Tanacan Atakan , Firat Oguz Esra , Anuk Ali Taner , Goncu Ayhan Sule , Neselioglu Salim , Sahin Dilek
Published: June 2021

It was aimed to evaluate the levels of maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in pregnant women with a fetus diagnosed with open neural tube defects (NTDs). This case‐control study included 38 pregnant women carrying fetuses with open NTDs and 44 age‐matched, pregnant women with no specified risk factors. Comparisons were made of the groups in respect of demographic and clinical data and PCSK9 levels. To examine the performance of PCSK9 levels in the prediction of fetal open NTDs, receiver operating characteristic (ROC) curve analysis was used. In the first and second trimesters, PCSK9 levels were determined to be lower in the NTD group than in the control group (p = 0.010 and p = 0.015, respectively). In the first trimester, the lower PCSK9 levels in the NTD group were not statistically significant (p = 0.575). In the second trimester, the ROC curve value with the best balance of sensitivity/specificity for PCSK9 was 71.9 ng/ml (84.6% sensitivity, 51.7% specificity) and in the first and second trimester combined, 74.4 ng/ml (81.6% sensitivity, 45.5% specificity) (p = 0.015, p = 0.036, respectively). PCSK9 may be involved in the etiopathogenesis of open NTDs at the critical steps of fetal neuronal differentiation. Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs.
Long‐term effectiveness of 6 mm micro‐rough implants in various indications: A 4.6‐ to 18.2‐year retrospective study
Authors: Raabe Clemens , Monje Alberto , Abou‐Ayash Samir , Buser Daniel , von Arx Thomas , Chappuis Vivianne
Published: June 2021

Objectives

To evaluate the long‐term effectiveness of 6 mm implants in various indications with a micro‐rough surface after 4.6–18.2 years in function and to assess key factors associated with implant survival, success, and biologic/technical complications.

Materials and methods

Fifty‐five patients with seventy‐four 6 mm implants placed from 2000 to 2013 attended the re‐examination assessing well‐established clinical and radiographic parameters, biologic and prosthetic complications, and patient‐reported outcome measures.

Results

Five implants were lost after a mean follow‐up period of 9.1 years resulting in a survival rate of 93.2%. All losses occurred in free‐end situations in the mandible. Smoking habit significantly reduced implant survival (hazard ratio 36.25). Two implants exhibited a history of peri‐implantitis, and one implant showed progressive marginal bone loss (MBL) resulting in a success rate of 89.2%. The mean MBL amounted to 0.029 mm. Increased MBL was found for implants placed in the maxilla (0.057 mm) and for implants with a diameter of 4.1 mm (0.043 mm). Soft tissue thickness (1.39 mm) and width of keratinized mucosa (1.91 mm) had no effect on MBL. Patient‐reported outcome measures showed high satisfaction (mean VAS scores 88%) and high quality of life (mean OHIP‐G14 score 2.2).

Conclusion

The present study demonstrated survival and success rates of 93.2% and 89.2% for 6 mm implants used in various indications. A factor leading to higher implant failure was smoking, whereas modulating factors increasing annual MBL included implants placed in the maxilla and implants with a diameter of 4.1 mm compared to 4.8 mm.
Cyclic nucleotide‐dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull–push sensitivity modulation
Authors: Dolzer Jan , Schröder Katrin , Stengl Monika
Published: June 2021

Olfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP‐ and adapt via cGMP‐dependent mechanisms. Perforated patch clamp recordings distinguished 11 currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K+ currents and two non‐specific cation currents. The Ca2+‐dependent K+ current IK(Ca2+) and the sensitive pheromone‐dependent K+ current IK(cGMP−), which both express fast kinetics, were inhibited by 8bcGMP, while a slow K+ current, IK(cGMP+), was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV‐reversing, non‐specific cation currents, ILL and Icat(PKC?), which remained activated in the presence of 8bcGMP. Their activations pull the membrane potential towards their 0‐mV reversal potentials, in addition to increasing intracellular Ca2+ levels voltage‐ and ILL‐dependently. Twenty minutes after application, 8bcGMP blocked a TEA‐independent K+ current, IK(noTEA), and a fast cation current, Icat(nRP), which both shift the membrane potential to negative values. We conclude that conditions of sensitization are maintained at high levels of cAMP, via specific opening/closure of ion channels that allow for fast kinetics, hyperpolarized membrane potentials, and low intracellular Ca2+ levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca2+‐permeable channels with slow kinetics that stabilize depolarized resting potentials. The antagonistic modulation of peripheral sensory neurons by cAMP or cGMP is reminiscent of pull–push mechanisms of neuromodulation at central synapses underlying metaplasticity.
Microglia proliferation plays distinct roles in acquired epilepsy depending on disease stages
Authors: Di Nunzio Martina , Di Sapia Rossella , Sorrentino Diletta , Kebede Valentina , Cerovic Milica , Gullotta Giorgia S. , Bacigaluppi Marco , Audinat Etienne , Marchi Nicola , Ravizza Teresa , Vezzani Annamaria
Published: June 2021

Objective

Microgliosis occurs in animal models of acquired epilepsy and in patients. It includes cell proliferation that is associated with seizure frequency and decreased neuronal cells in human epilepsy. The role of microglia proliferation in the development of acquired epilepsy is unknown; thus, we examined its contribution to spontaneous seizure, neurodegeneration, and cognitive deficits in different disease phases.

Methods

We used a model of acquired epilepsy triggered by intra‐amygdala kainic acid in C57BL6N adult male mice. Mice were electroencephalographically (EEG) monitored (24/7) during status epilepticus and in early and chronic disease. Microglia proliferation was blocked by GW2580, a selective CSF1 receptor inhibitor, supplemented in the diet for 21 days from status epilepticus onset. Then, mice were returned to placebo diet until experiment completion. Control mice were exposed to status epilepticus and fed with placebo diet. Experimental mice were tested in the novel object recognition test (NORT) and in Barnes maze, and compared to control and sham mice. At the end of the behavioral test, mice were killed for brain histopathological analysis. Additionally, seizure baseline was monitored in chronic epileptic mice, then mice were fed for 14 days with GW2580 or placebo diet under 24/7 EEG recording.

Results

GW2580 prevented microglia proliferation in mice undergoing epilepsy, whereas it did not affect microglia or basal excitatory neurotransmission in the hippocampus of naive mice. Mice with occluded microglia proliferation during early disease development underwent status epilepticus and subsequent epilepsy similar to placebo diet mice, and were similarly impaired in NORT, with improvement in Barnes maze. GW2580‐treated mice displayed neuroprotection in the hippocampus. In contrast, blockade of microglia proliferation in chronic epileptic mice resulted in spontaneous seizure reduction versus placebo mice.

Significance

Microglia proliferation during early disease contributes to neurodegeneration, whereas in late chronic disease it contributes to seizures. Timely pharmacological interference with microglia proliferation may offer a potential target for improving disease outcomes.
Rapid evolution of knockdown resistance haplotypes in response to pyrethroid selection in Aedes aegypti
Authors: Baltzegar Jennifer , Vella Michael , Gunning Christian , Vasquez Gissella , Astete Helvio , Stell Fred , Fisher Michael , Scott Thomas W. , Lenhart Audrey , Lloyd Alun L. , Morrison Amy , Gould Fred
Published: June 2021

This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance‐conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.
Are We Modelling Spatially Varying Processes or Non‐linear Relationships?
Authors: Sachdeva Mehak , Fotheringham A. Stewart , Li Ziqi , Yu Hanchen
Published: June 2021

Studies of spatially varying parameter estimates obtained in the calibration of various types of local statistical models are commonplace. The variation in such estimates is typically explained in terms of spatially varying processes. This paper highlights that an alternative explanation for spatially varying parameter estimates, in terms of non‐linearity, should be examined prior to relating such variation to spatially varying processes. This can be achieved by a simple screening procedure which is described and demonstrated and which can easily be applied to the results of any local model. The problem is highlighted, and the solution demonstrated, with a set of simulated data and then with a real‐world data set. The paper also highlights the obverse situation whereby the inappropriate application of a GAM produces spurious nonlinear results when the real relationships are linear but spatially varying.
Patients’ and parents’ satisfaction with, and preference for, haemophilia A treatments: a cross‐sectional, multicentre, observational study
Authors: Park Young Shil , Hwang Tai Ju , Cho Goon Jae , Kim Soon Ki , Park Sang Kyu , Kim Ji Yoon , Baek Hee Jo , Kim Young‐Joo , Lee Ho‐Jin , Shin Ji‐Soo , Nam Chung‐Mo , Sun Jiyu , Yoo Ki Young
Published: June 2021

Introduction

Reports on patients’ satisfaction and preferred characteristics for treatments would be worthwhile when choosing an optimal treatment reflecting patients’ perspectives.

Aim

To identify the characteristics and treatment patterns of patients with haemophilia A, or their caregivers, in Korea and explore patient preferences and satisfaction with their treatment.

Methods

This cross‐sectional, multicentre, observational study was conducted from April 2018 to September 2019 at six nationwide hospitals and three Korea Hemophilia Foundation clinics. Patients aged ≥16 years, or legal caregivers of paediatric patients, who had used factor VIII (FVIII) concentrates for ≥1 month were enrolled. Satisfaction with treatment was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM); preference was evaluated using discrete choice experiment (DCE), with 10 series of two hypothetical treatment options created from D‐efficient block design, which varied across five attributes.

Results

Overall, 505 patients (mean age 31 years) were enrolled in the study. Patients had received FVIII concentrate for an average of 102.9 months (prophylaxis: 53.5%; on‐demand: 22.2%). Mean TSQM scores were 64.6 (effectiveness domain), 97.9 (side effects), 57.1 (convenience) and 66.8 (global satisfaction). The number of vials per injection, and the frequency of drug administration, was significantly associated with treatment satisfaction. According to DCE, simpler treatment options were preferred by patients/caregivers.

Conclusion

The lowest satisfaction levels were shown in the treatment convenience domain. Patients/parents preferred simpler and easier treatment characteristics. In an attempt to enhance the overall satisfaction of patients and caregivers with treatment, consideration of more convenient characteristics is required in future decisions regarding treatment selection.
Digital reminiscence app co‐created by people living with dementia and carers: Usability and eye gaze analysis
Authors: Boyd Kyle , Bond Raymond , Ryan Assumpta , Goode Deborah , Mulvenna Maurice
Published: June 2021

Background

This research reports on a pilot study that examined the usability of a reminiscence app called ‘InspireD’ using eye tracking technology. The InspireD app is a bespoke digital intervention aimed at supporting personalized reminiscence for people living with dementia and their carers. The app was developed and refined in two co‐creation workshops and subsequently tested in a third workshop using eye tracking technology.

Intervention

Eye tracking was used to gain insight into the user's cognition since our previous work showed that the think‐aloud protocol can add to cognitive burden for people living with dementia while also making the test more unnatural.

Results

Results showed that there were no barriers to using a wearable eye tracker in this setting and participants were able to use the reminiscence app freely. However, some tasks required prompts from the observer when difficulties arose. While prompts are not normally used in usability testing (as some argue the prompting defeats the purpose of testing), we used ‘prompt frequency’ as a proxy for measuring the intuitiveness of the task. There was a correlation between task completion rates and prompt frequency. Results also showed that people living with dementia had fewer gaze fixations when compared to their carers. Carers had greater fixation and saccadic frequencies when compared to people living with dementia. This perhaps indicates that people living with dementia take more time to scan and consume information on an app. A number of identified usability issues are also discussed in the paper.

Patient or Public Contribution

The study presents findings from three workshops which looked at user needs analysis, feedback and an eye tracking usability test combined involving 14 participants, 9 of whom were people living with dementia and the remaining 5 were carers.
Violence, Control and Restraint: The Harms to Young Adults Particularly Upon Transition
Authors: PRICE JAYNE
Published: June 2021

The transition into the young adult/adult estate at age 18 years is marked by a significant loss of provision and shift in institutional treatment. One of the many harms endured is the change in restraint which is harmful and damaging yet prevailing. The data presented here show how the distinct needs of this vulnerable population are widely overlooked. This article extends the literature regarding young adults and argues that there should be greater exploration and understanding of their behaviour and the impacts of transitions. This, in turn, leads to recommendations for changes to practices within the young adult/adult estate.
CONSISTENT EXPECTATIONS EQUILIBRIA IN MARKOV REGIME SWITCHING MODELS AND INFLATION DYNAMICS
Authors: Airaudo Marco , Hajdini Ina
Published: June 2021

We study the existence of Stochastic Consistent Expectations Equilibria (SCEE) in linear Markov regime switching models. An SCEE exists when the model‐implied mean and first‐order autocorrelation coincide with those predicted by the agents via misspecified forecasting rules. For a simple regime‐switching monetary policy model, the parametric space where at least one SCEE exists is rather wide, and may extend well beyond the rational expectations equilibrium determinacy frontier. Misspecified expectations combined with regime switching yield a strong endogenous amplification mechanism that help generate the near unit root dynamics for inflation observed in the United States before the Great Moderation.
Endogenous proteases in giant freshwater prawn (Macrobrachium rosenbergii): changes and its impacts on texture deterioration during frozen storage
Authors: Jiang Qixing , Gao Pei , Liu Jiatong , Yu Dawei , Xu Yanshun , Yang Fang , Wang Bin , Yu Peipei , Xia Wenshui
Published: June 2021

Effects of endogenous enzymes on texture deterioration of Macrobrachium rosenbergii during frozen storage (−18 °C) were investigated. The prawn was pretreated with iodoacetic acid (IAA) solution to inhibit cysteine proteases and/or phenylmethylsulfonyl fluoride (PMSF) solution to inhibit trypsin before frozen storage, and sterile distilled water was used as the control. After 16 weeks of cryopreservation, the shear force of the groups treated with enzyme inhibitors was significantly higher than that of sterile distilled water‐treated group (control; P < 0.05), while significantly fewer TCA‐dissolved peptides, α‐amino nitrogen and Myofibril fragmentation index (MFI) value were observed in all inhibitor‐treated groups (P < 0.05). Compared with PMSF treatment, IAA or IAA + PMSF treatment effectively alleviated softening and remarkably reduced the accumulation of TCA‐soluble peptides and AAN (α‐amino nitrogen) during frozen storage, with a lower MFI value and a higher sodium dodecyl sulphate‐polyacrylamide gel electrophoresis band intensity. Therefore, endogenous cysteine proteases in muscle play a crucial part in texture deterioration of giant freshwater prawn during cryopreservation.