bluuebunny/crossref_metadata_2025 huggingface dataset:
Key criteria for selecting green suppliers for construction projects in the UAE
Authors: Asaad AbdulRahman , El-Sayegh Sameh Monir
Published: April 2021

Purpose

This paper aims to identify and assess the key criteria for selecting green suppliers in the United Arab Emirates (UAE) construction industry.

Design/methodology/approach

A total of 20 criteria were identified and shortlisted through an extensive literature review. These criteria were grouped into four categories: technical and commercial bid, company characteristics, environmental and socioeconomic. A questionnaire was then developed and distributed to construction professionals in the UAE. A total of 39 professionals responded to the survey including contractors, consultants, owners and suppliers. The respondents performed pairwise comparisons among the selection criteria. Data was then analyzed using the Expert Choice Software.

Findings

The research findings highlighted that the technical and commercial bid category was ranked as the most important with a weight of 0.338, followed by socioeconomic, company characteristics and environmental categories weighing 0.239, 0.225 and 0.199, respectively. The UAE construction professionals also ranked health and safety, material’s quality and tender price as the top three most important criteria when selecting a sustainable supplier.

Practical implications

This research addresses the lack of literature toward green supplier selection in the UAE. In addition, it assists contractors in selecting the appropriate supplier and promotes sustainable practices in the construction industry.

Originality/value

Material suppliers play an important role in the successful delivery of construction projects. Selecting the appropriate supplier is of paramount importance to project success. Several methods can be used to evaluate and select the best-fit suppliers. However, the selection criteria in such methods are primarily based on traditional construction projects rather than sustainable construction projects. Recently, there is an increase in the number of sustainable construction projects in the UAE. Therefore, identifying and assessing the key criteria for selecting green suppliers is needed. This paper fills the gap in literature as to selecting green suppliers in construction projects.
Digital skills in tourism. A study from the Next Tourism Generation (NTG) Alliance
Authors: Zaragoza-Sáez Patrocinio , Marco-Lajara Bartolomé , Ubeda-Garcia Mercedes
Published: April 2021

Purpose

This paper aims to identify the gap existing between the current and future needs regarding digital skills, as well as the training needs for the 2030 horizon in Spanish tourism organisations belonging to five subsectors (accommodation, food and beverage, destination management, visitor attractions and travel agents and tour operators).

Design/methodology/approach

A mixed research methodology, which combined qualitative and quantitative approaches, served as the basis for this research work. Qualitative research took place between April 2018 and March 2019 and went through three stages: desk research, focus groups and interviews. Quantitative research developed from January to June 2019 by means of an online administered survey (Qualtrics). In total, 139 Spanish tourism organisations participated.

Findings

Tourism organisations analysed consider that digital skills are still an unresolved issue. Employees are willing to operate in environments where technology has an increasingly leading role. However, organisations believe that there remains a lot to be done until employees have, both at present and by the year 2030, a suitable level of digital skills enabling them to operate in the tourism subsectors analysed.

Originality/value

This study is framed within the European project called Next Tourism Generation (NTG), which involves 14 partners from eight countries. The findings obtained will help to develop a Europe Blueprint Strategy for digital skills within the tourism and hospitality sector, to provide employees, employers, entrepreneurs, teachers, trainers and students with a set of core digital skills represented in a skills matrix.
The role of detective experience on homicide clearances
Authors: Goodison Sean E.
Published: April 2021

Purpose

The study aims to examine the effect of detective experience on the likelihood of clearing a homicide, while controlling for additional extralegal and case/investigative characteristics.

Design/methodology/approach

This study uses homicide and policing data collected from case files in a mid-sized US city. Detective experience is measured in multiple ways. Analytical models include extralegal variables, case characteristics, and proxies of investigative quality as controls. The study uses logistic regression with a dichotomous clearance outcome.

Findings

The results suggest a robust and significant inverse relationship between the years spent as a homicide detective and the likelihood of case closure. However, years of experience with the department overall has a significant and positive relationship to clearance. Investigation-related variables and case characteristics contribute more to model explanatory power than extralegal factors.

Originality/value

The potential role of experience has not been fully explored, with contradictory findings over time. This work builds on previous research to highlight the potential role of experience in clearing cases, while questioning previous assumptions tied to the belief that more experience improves investigative outcomes.
Studies on fatty acid profile and microstructure of butter, dairy fat spreads and blended spreads produced in Russia
Authors: Smykov Igor T , Topnikova Elena V , Danilova Ekaterina S
Published: April 2021

This paper examines the features of the production of butter and spreads in the Russian Federation. It was found that the fatty acid profile of the cows' milk of the Yaroslavl breed does not differ significantly in comparison with the milk of the more widespread breeds in the world. It is shown that when using different methods of butter production, there are differences in the butter microstructure. It is noted that the use of the concentration and phase reversal method for the production of butter and spreads can be accompanied by the formation of eutectic mixtures of fatty acids.
Spatial clustering of willingness to pay for ecosystem services
Authors: Toledo‐Gallegos Valeria M. , Long Jed , Campbell Danny , Börger Tobias , Hanley Nick
Published: April 2021

Variations of willingness to pay (WTP) in geographical space have been characterised by the presence of localised patches of higher and lower values. However, to date, spatial valuation studies have not explored whether the distribution of hot (cold) spots of WTP is particular to each environmental good or if it follows similar patterns to other, comparable, environmental goods. We address this question by contrasting the spatial patterns of hot (cold) clusters of WTP for improvements in several ecosystem services. We geocoded individual‐specific WTP estimates derived from a discrete choice experiment exploring preferences for ecosystem service improvements for three different catchment areas in Scotland comprising urban, agricultural, riverine and estuarine ecosystems. The local Moran's I statistic was used to find statistically significant local clusters and identify hot spots and cold spots. Finally, Multi‐type Ripley's K and L functions were used to contrast the spatial patterns of local clusters of WTP among ecosystem services, and across case studies. Our results show that hotspots of WTP for environmental improvements tend to occur close to each other in space, regardless of the ecosystem service or the area under consideration. Our findings suggest that households sort themselves according to their preferences for estuarine ecosystem services.
Sustainable biosynthesis of chemicals from methane and glycerol via reconstruction of multi‐carbon utilizing pathway in obligate methanotrophic bacteria
Authors: Le Hoa Thi Quynh , Nguyen Anh Duc , Park Ye Rim , Lee Eun Yeol
Published: April 2021

Obligate methanotrophic bacteria can utilize methane, an inexpensive carbon feedstock, as a sole energy and carbon substrate, thus are considered as the only nature‐provided biocatalyst for sustainable biomanufacturing of fuels and chemicals from methane. To address the limitation of native C1 metabolism of obligate type I methanotrophs, we proposed a novel platform strain that can utilize methane and multi‐carbon substrates, such as glycerol, simultaneously to boost growth rates and chemical production in Methylotuvimicrobium alcaliphilum 20Z. To demonstrate the uses of this concept, we reconstructed a 2,3‐butanediol biosynthetic pathway and achieved a fourfold higher titer of 2,3‐butanediol production by co‐utilizing methane and glycerol compared with that of methanotrophic growth. In addition, we reported the creation of a methanotrophic biocatalyst for one‐step bioconversion of methane to methanol in which glycerol was used for cell growth, and methane was mainly used for methanol production. After the deletion of genes encoding methanol dehydrogenase (MDH), 11.6 mM methanol was obtained after 72 h using living cells in the absence of any chemical inhibitors of MDH and exogenous NADH source. A further improvement of this bioconversion was attained by using resting cells with a significantly increased titre of 76 mM methanol after 3.5 h with the supply of 40 mM formate. The work presented here provides a novel framework for a variety of approaches in methane‐based biomanufacturing.
Chromosome‐level genome assembly of the Arctic fox (Vulpes lagopus) using PacBio sequencing and Hi‐C technology
Authors: Peng Yongdong , Li Hong , Liu Zhengzhu , Zhang Chuansheng , Li Keqiang , Gong Yuanfang , Geng Liying , Su Jingjing , Guan Xuemin , Liu Lei , Zhou Ruihong , Zhao Ziya , Guo Jianxu , Liang Qiqi , Li Xianglong
Published: April 2021

The Arctic fox (Vulpes lagopus) is the only fox species occurring in the Arctic and has adapted to its extreme climatic conditions. Currently, the molecular basis of its adaptation to the extreme climate has not been characterized. Here, we applied PacBio sequencing and chromosome structure capture technique to assemble the first V. lagopus genome assembly, which is assembled into chromosome fragments. The genome assembly has a total length of 2.345 Gb with a contig N50 of 31.848 Mb and a scaffold N50 of 131.537 Mb, consisting of 25 pseudochromosomal scaffolds. The V. lagopus genome had approximately 32.33% repeat sequences. In total, 21,278 protein‐coding genes were predicted, of which 99.14% were functionally annotated. Compared with 12 other mammals, V. lagopus was most closely related to V. Vulpes with an estimated divergence time of ~7.1 Ma. The expanded gene families and positively selected genes potentially play roles in the adaptation of V. lagopus to Arctic extreme environment. This high‐quality assembled genome will not only promote future studies of genetic diversity and evolution in foxes and other canids but also provide important resources for conservation of Arctic species.
Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma
Authors: Watanabe Kageaki , Okuma Yusuke , Kawai Shoko , Nagamata Makoto , Hosomi Yukio
Published: April 2021

Background

Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next‐generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM.

Methods

Eligible patients with MPM having adequate organ function and a performance status of 0–2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1–3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression‐free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints.

Results

This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2–11.2) months, and the median OS was 9.1 (range, 6.2–22.0) months. The median number of treatment cycles was three (range, 2–11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.

Conclusions

Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.
Longitudinal changes in skeletal muscle mass in patients with advanced squamous cell lung cancer
Authors: Lee Jongsoo , Kim Eun Young , Kim Eunji , Kim Kwang Gi , Kim Young Jae , Kim Young Saing , Ahn Hee Kyung , Lee Sang‐Woong
Published: April 2021

Background

Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC).

Methods

This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross‐sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2/m2 in men and < 29 cm2/m2 in women.

Results

The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9–11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2/month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001).

Conclusions

Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life.
Alterations in connectivity of the bed nucleus of the stria terminalis during early abstinence in individuals with alcohol use disorder
Authors: Flook Elizabeth A. , Feola Brandee , Benningfield Margaret M. , Silveri Marisa M. , Winder Danny G. , Blackford Jennifer Urbano
Published: April 2021

Background

For individuals with Alcohol Use Disorder (AUD), long‐term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety‐like behaviors during abstinence, particularly in female mice. Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions. To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap.

Methods

Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan. BNST structural connectivity was evaluated using probabilistic tractography. A linear mixed model was used to test between‐groups differences in BNST network connectivity. Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group. Sex was included as a factor for all analyses.

Results

The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men. Women also showed region‐specific differences, with stronger BNST‐hypothalamus structural connectivity but weaker vmPFC‐BNST structural connectivity than men. Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC‐BNST structural connectivity that was moderated by sex.

Conclusions

This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences. The sex‐specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex‐specific treatments.
Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta‐analysis
Authors: Hahn Judith A. , Murnane Pamela M. , Vittinghoff Eric , Muyindike Winnie R. , Emenyonu Nneka I. , Fatch Robin , Chamie Gabriel , Haberer Jessica E. , Francis Joel M. , Kapiga Saidi , Jacobson Karen , Myers Bronwyn , Couture Marie Claude , DiClemente Ralph J. , Brown Jennifer L. , So‐Armah Kaku , Sulkowski Mark , Marcus Gregory M. , Woolf‐King Sarah , Cook Robert L. , Richards Veronica L. , Molina Patricia , Ferguson Tekeda , Welsh David , Piano Mariann R. , Phillips Shane A. , Stewart Scott , Afshar Majid , Page Kimberly , McGinnis Kathleen , Fiellin David A. , Justice Amy C. , Bryant Kendall , Saitz Richard
Published: April 2021

Background

Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self‐reported alcohol use, we conducted an individual participant data (IPD) meta‐analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self‐reporting unhealthy alcohol consumption.

Methods

We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1‐step IPD meta‐analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index—BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger‐prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self‐reported alcohol use using the AUDIT‐C score.

Results

One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT‐C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.

Conclusions

Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.
Resilience of global and local value chains to the Covid‐19 pandemic: Survey evidence from vegetable value chains in Senegal
Authors: Van Hoyweghen Kaat , Fabry Anna , Feyaerts Hendrik , Wade Idrissa , Maertens Miet
Published: April 2021

In this paper we descriptively investigate the Covid‐19 pandemic's early impact on the fruit and vegetable supply chain in Senegal, using trade statistics and survey data collected through online questionnaires and telephone interviews with smallholder farmers, agro‐industrial companies, agricultural workers, traders, importers, and consumers. Our results point to major differences in how Covid‐19 and containment measures disrupt supply chains between the modern export‐oriented supply chain that is centered around a few large vertically integrated agro‐industrial companies, and the more traditional domestic‐oriented supply chain with a large number of smallholder farmers and informal traders—with the former being more resilient to the Covid‐19 shock. We show that both the modern and the traditional supply chain innovate to cope with the Covid‐19 containment measures. While our study is subject to some limitations, our findings bring nuance in the debate on the resilience of the food system to the pandemic, and have important policy and research implications toward international trade, social safety measures, and food and nutrition security.
Population structure and relatedness estimates in a Mexican sample
Authors: Colistro V. , Rojas‐Martínez A. , Carracedo A. ,   CHIBCHA Consortium, Tomlinson I. , Carvajal‐Carmona L. , Cruz R. , Sans M.
Published: April 2021

Population stratification (PS) is a confounding factor in genome‐wide association studies (GWASs) and also an interesting process itself. Latin American populations have mixed genetic ancestry, which may account for PS. We have analyzed the relatedness, by means of the identity‐by‐descent (IBD) estimations, in a sample of 1805 individuals and 1.006.703 autosomal mutations from a case–control study of colorectal cancer in Mexico. When using the recommended protocol for quality control assessment, 402 should have been removed due to relatedness. Our purpose was to analyze this value in the context of an admixed population. For that aim, we reanalyzed the sample using two software designed for admixed populations, obtaining estimates of 110 and 70 related individuals to remove. The results showed that the first estimation of relatedness was an effect of the higher Native American contribution in part of the data samples, being a confounding factor for IBD estimations. We conclude in the importance of considering PS and genetic ancestry in order to avoid spurious results, not only in GWAS but also in relatedness analysis.
The bioethics of loneliness
Authors: Lederman Zohar
Published: April 2021

This article poses an invitation for bioethicists to engage with loneliness as a bioethics and public health concern. I argue that loneliness is a relevant issue for bioethicists for three main reasons: it causes ill‐health; particularly in the age of Covid‐19, it is becoming prominent on the clinical and public health agenda, affecting millions worldwide; and it engenders several ethical and philosophical questions as a social determinant of health with a rich conceptual background. In what follows I first review the link between loneliness and ill‐health and argue that it should concern bioethicists because of this link. I also demonstrate how pertinent the issue of loneliness is being considered nowadays, and mark this as another reason for bioethicists to become engaged. I then move on to define loneliness and its various forms, drawing from modern and contemporary philosophers. The way we choose to cope with the pandemic of loneliness depends in part on its theoretical underpinnings, as well as its empirical scope. Theory thus combines with empirical data in order to devise and implement a rational public health policy, necessitating the kind of interdisciplinary approach that is the bedrock of bioethics. I conclude by suggesting future areas of research and recommendations.
Development of a shared decision-making tool in vitiligo: an international study
Authors: Shourick J. , Ahmed M. , Seneschal J. , Passeron T. , Andreux N. , Qureshi A. , Chow E.Y. , Natella P.A. , Harris J. , Tran V.-T. , Ezzedine K.
Published: April 2021

Background

Shared decision-making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology.

Objectives

To develop and validate a SDMt for use in specialized consultation for vitiligo.

Methods

A prospective cross-sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision-making in the setting of a specialized consultation for vitiligo using an anchored-theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e-Delphi method.

Results

We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision-making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English.

Conclusions

We developed a tool for shared decision-making in nonsegmental vitiligo, which we translated and cross-culturally validated in a US patient population with vitiligo to ensure its generalizability.
Robot‐assisted Boari flap and psoas hitch ureteric reimplantation: technique insight and outcomes of a case series with ≥1 year of follow‐up
Authors: Dell’Oglio Paolo , Palagonia Erika , Wisz Pawel , Andras Iulia , De Groote Ruben , Poelaert Filip , Beato Sergi , Goossens Marijn , Schatteman Peter , D’Hondt Frederiek , De Naeyer Geert , Mazzone Elio , Mottrie Alexandre ,   the ERUS Educational Working Group, the YAU Working Group on Robot‐Assisted Surgery
Published: April 2021

Objective

To describe step‐by‐step surgical techniques and report outcomes of the largest single‐centre series of patients with distal ureteric disease exclusively treated with robot‐assisted ureteric reimplantation with Boari flap (RABFUR) and psoas hitch (RAPHUR), with a minimum follow‐up of 1 year and complete postoperative data.

Patients and Methods

A total of 37 patients with distal ureteric disease were treated between 2010 and 2018. Of these, 81% and 19% underwent RAPHUR and RABFUR, respectively. Intra‐, peri‐ and postoperative outcomes were assessed. The 90‐day postoperative complications were reported according to the standardised methodology proposed by the European Association of Urology Ad Hoc Panel. Functional outcomes (creatinine, estimated glomerular filtration rate [eGFR]) and postoperative symptoms (visual analogue pain scale) were assessed.

Results

The median operating time and blood loss were 180 min and 100 mL, respectively. There were no conversions to open surgery and no intraoperative transfusions. The median length of stay, bladder catheter indwelling time and stent removal were 4, 7 and 30 days, respectively. The median follow‐up was 24 months. Overall, 10 patients (27%) had postoperative complications and of these, eight (22%) and two (5.4%) were Clavien–Dindo Grade I–II and III, respectively. At the last follow‐up, the median postoperative creatinine level and eGFR were 0.9 mg/dL and 73.5 mL/min/1.73 m2, respectively. At the last follow‐up, five (13.5%) and three (8%) patients had Grade 1 hydronephrosis and mild urinary symptoms, respectively. The study limitations include its retrospective nature.

Conclusion

In the present study, we present our RABFUR and RAPHUR techniques. We confirm the feasibility and safety profile of both approaches in patients with distal ureteric disease relying on the largest single‐centre series with ≥1 year of follow‐up.
Measuring mania‐like elevated mood through amphetamine‐induced 50‐kHz ultrasonic vocalizations in rats
Authors: Wöhr Markus
Published: April 2021

Rats emit 50‐kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50‐kHz USV are elicited by the psychostimulant d‐amphetamine. Exaggerated 50‐kHz USV emission evoked by d‐amphetamine is modulated by dopamine, noradrenaline and 5‐hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti‐manic drug for treating bipolar disorder. This indicates that exaggerated 50‐kHz USV emission can serve as a reliable and valid measure for assessing mania‐like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti‐manic pharmacological interventions on a broader range of behaviours by including exaggerated 50‐kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania.

LINKED ARTICLES

This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc
Humoral immune responses to AAV gene therapy in the ocular compartment
Authors: Whitehead Michael , Osborne Andrew , Yu‐Wai‐Man Patrick , Martin Keith
Published: April 2021

Viral vectors can be utilised to deliver therapeutic genes to diseased cells. Adeno‐associated virus (AAV) is a commonly used viral vector that is favoured for its ability to infect a wide range of tissues whilst displaying limited toxicity and immunogenicity. Most humans harbour anti‐AAV neutralising antibodies (NAbs) due to subclinical infections by wild‐type virus during infancy and these pre‐existing NAbs can limit the efficiency of gene transfer depending on the target cell type, route of administration and choice of serotype. Vector administration can also result in de novo NAb synthesis that could limit the opportunity for repeated gene transfer to diseased sites. A number of strategies have been described in preclinical models that could circumvent NAb responses in humans, however, the successful translation of these innovations into the clinical arena has been limited. Here, we provide a comprehensive review of the humoral immune response to AAV gene therapy in the ocular compartment. We cover basic AAV biology and clinical application, the role of pre‐existing and induced NAbs, and possible approaches to overcoming antibody responses. We conclude with a framework for a comprehensive strategy for circumventing humoral immune responses to AAV in the future.
Opting out and topping up reconsidered: Informal care under uncertain altruism
Authors: Canta Chiara , Cremer Helmuth
Published: April 2021

We study the design of public long‐term care (LTC) insurance when the altruism of informal caregivers is uncertain. We consider non‐linear policies where the LTC transfer depends on the level of informal care, which is assumed to be observable, while children's altruism is not. Our policy encompasses two policies traditionally considered in the literature: topping up policies consisting of a transfer independent of informal care, and opting out policies entailing a positive transfer only if children fail to provide care. We show that both total and informal care should increase with the children's level of altruism. This is obtained under full and asymmetric information. Public LTC transfers, on the other hand, may be non‐monotonic. Under asymmetric information, public LTC transfers are lower than their full information level for the parents whose children are the least altruistic, while it is distorted upward for the highest level of altruism. This is explained by the need to provide incentives to highly altruistic children. In contrast to both topping up and opting out policies, the implementing contract is always such that social care increases with informal care.
How does land titling affect credit demand, supply, access, and rationing: Evidence from China
Authors: Cheng Wenli , Zhou Nan , Zhang Longyao
Published: April 2021

Based on official survey data from the Chinese Ministry of Agriculture and Rural Affairs collected in 2010 and 2015, we use the difference‐in‐differences method to study how the Chinese land titling reform beginning in 2009 in tiers (“the Reform”) affected the demand, supply, access, and rationing on the Chinese rural credit market. Our main findings are: (1) the Reform increased households’ hidden credit demand, but not their effective credit demand; (2) the Reform had no significant effect on effective credit supply or a household's credit access; (3) the Reform increased the likelihood of non‐price credit rationing, in particular risk rationing; and (4) in the subsample of households living in counties where the local governments explicitly permitted the use of land as collateral, the Reform had a positive effect on credit supply; but in the subsample of households living in counties where land collateral was not explicitly permitted, the Reform was associated with an increase in non‐price rationing. Findings of this study are not only useful to assess the economic and social implications of rural land titling in China, but they also offer insights in understanding similar policies in other countries, particularly developing economies.
Oral intake of Lactobacillus plantarum L‐14 extract alleviates TLR2‐ and AMPK‐mediated obesity‐associated disorders in high‐fat‐diet‐induced obese C57BL/6J mice
Authors: Lee Jaehoon , Park Sangkyu , Oh Naeun , Park Jaehyun , Kwon Mijin , Seo Jeongmin , Roh Sangho
Published: April 2021

Objectives

Whether periodic oral intake of postbiotics positively affects weight regulation and prevents obesity‐associated diseases in vivo is unclear. This study evaluated the action mechanism of Lactobacillus plantarum L‐14 (KTCT13497BP) extract and the effects of its periodic oral intake in a high‐fat‐diet (HFD) mouse model.

Materials and methods

Mouse pre‐adipocyte 3T3‐L1 cells and human bone marrow mesenchymal stem cells (hBM‐MSC) were treated with L‐14 extract every 2 days during adipogenic differentiation, and the mechanism underlying anti‐adipogenic effects was analysed at cellular and molecular levels. L‐14 extract was orally administrated to HFD‐feeding C57BL/6J mice every 2 days for 7 weeks. White adipose tissue was collected and weighed, and liver and blood serum were analysed. The anti‐adipogenic mechanism of exopolysaccharide (EPS) isolated from L‐14 extract was also analysed using Toll‐like receptor 2 (TLR2) inhibitor C29.

Results

L‐14 extract inhibited 3T3‐L1 and hBM‐MSC differentiation into mature adipocytes by upregulating AMPK signalling pathway in the early stage of adipogenic differentiation. The weight of the HFD + L‐14 group (31.51 ± 1.96 g) was significantly different from that of the HFD group (35.14 ± 3.18 g). L‐14 extract also significantly decreased the serum triacylglycerol/high‐density lipoprotein cholesterol ratio (an insulin resistance marker) and steatohepatitis. In addition, EPS activated the AMPK signalling pathway by interacting with TLR2, consequently inhibiting adipogenesis.

Conclusions

EPS from L‐14 extract inhibits adipogenesis via TLR2 and AMPK signalling pathways, and oral intake of L‐14 extract improves obesity and obesity‐associated diseases in vivo. Therefore, EPS can be used to prevent and treat obesity and metabolic disorders.
Why did the butler do it?
Authors: White Justin F.
Published: April 2021

Drawing on contemporary agency theory and the phenomenological–existential tradition, this paper uses Mr. Stevens, the narrator‐butler of Kazuo Ishiguro'sThe Remains of the Day, to examine the interplay and potential tensions between different aspects (and thus different standards) of human agency. Highlighting the problem of mission creep described by John Martin Fischer, in which a notion expands beyond the original purpose, I use Stevens's thoughts on dignity to outline three different ways actions can (or can fail to) trace back to agents—autonomy as self‐control, authenticity as sincerity, and authenticity as ownership. I then propose that the way Stevens embraces and acts consistently within his subservient professional role (autonomy as self‐control) weakens his ability to take responsibility for his life in the sense required by authenticity as ownership. Because the self‐responsibility of authenticity requires normative flexibility (the ability to revise and reshape one's commitments and values), when normatively inflexible agents act in self‐controlled ways according to their roles or welfare standards, they may limit their ability to take responsibility for their lives. In addition to illuminating debates about whether robust human agency is compatible with subservience, the normative flexibility involved in authenticity has implications for human agency more broadly.
Clinical and radiological activity of secondary progressive multiple sclerosis in a population‐based cohort
Authors: Mathey Guillaume , Ancel Thomas , Garot Teresa , Soudant Marc , Pittion‐Vouyovitch Sophie , Guillemin Francis , Debouverie Marc , Epstein Jonathan
Published: April 2021

Background and purpose

Patients with secondary progressive multiple sclerosis (SP MS) and clinical and/or radiological activity could be the more likely to benefit from disease‐modifying treatments. To evaluate the proportions each year after progression onset, patients with SP MS onset between 2002 and 2012 from a population‐based multiple sclerosis registry in northeastern France were studied.

Methods

Progression onset was first identified by the neurologist's diagnosis (N cohort), and then by using an automated data‐driven definition (D cohort). In a given year after onset of progression, clinical activity was defined as at least one relapse, and radiological activity as at least one new T2 and/or gadolinium‐enhancing lesion. A multivariate mixed logistic regression was used to assess factors associated with activity during the year.

Results

In the N cohort, amongst 833 patients with SP MS with a median follow‐up of 8 years, 10.0%–14.8% had at least one relapse in a year during the first 5 years of progression. Including both clinical and radiological activity increased these proportions to 11.9%–23.7%, with the proportion having a magnetic resonance imaging scan in the year ranging from 29.8% to 40.5%. The first year of progression, a young age and a high relapse rate during the 5 years before progression were associated with activity in a given year. The D cohort results confirmed these findings.

Conclusions

A substantial proportion of patients with SP MS present disease activity. Further studies should evaluate the impact of disease‐modifying treatments on the disease course of these patients.
The impact of IPSAS adoption on corruption in developing countries
Authors: Tawiah Vincent
Published: April 2021

This paper investigates whether the International Public Sector Accounting Standards (IPSAS) is a potential enabler or constrainer of corruption in developing countries. We employ the System Generalised Method of Moments on a sample of 77 developing countries between 2005 and 2017. We find that IPSAS is negatively and significantly associated with corruption, suggesting that the adoption of IPSAS helps in controlling corruption in developing countries. The results still hold after accounting for IPSAS experience and the adoption of other international accounting standards. However, in further analyses, we find that negative impact of IPSAS on corruption is more pronounced for countries that have fully adopted the accrual‐based IPSAS. This study, therefore, provides evidence to policymakers on why developing countries should adopt IPSAS, especially in the fight against corruption.
The Pseudomonas aeruginosa PAAR2 cluster encodes a putative VRR‐NUC domain‐containing effector
Authors: Wang Shuangyue , Geng Zhi , Zhang Heng , She Zhun , Dong Yuhui
Published: April 2021

The bacterial type VI secretion system (T6SS) secretes many toxic effectors to gain advantage in inter‐bacterial competition and for eukaryotic host infection. The cognate immunity proteins of these effectors protect bacteria from the virulence of their own effectors. The T6SS injects its inner‐needle Hcp tube, the sharpening tip complex ‐consisting of VgrG and proline‐alanine‐alanine‐arginine repeats (PAAR) proteins‐ and toxic effectors into neighboring cells. Its functions are largely determined by the activities of its delivered effectors. Five PAAR proteins were found in the Pseudomonas aeruginosa PAO1 genome with three of them shown to facilitate the delivery of various effectors. Here, we report a putative virus‐type replication‐repair nuclease domain‐containing effector TseV encoded by the least investigated P. aeruginosa PAAR2 cluster. The crystal structure of its putative cognate effector TsiV is presented at 1.6 Å resolution. Through structure and sequence comparisons, we propose TseV‐TsiV to be a putative novel effector–immunity (E‐I) pair and we discuss the roles of other PAAR2 cluster encoded proteins.
Navigating dietary advice for multiple sclerosis
Authors: Russell Rebecca D. , Black Lucinda J. , Begley Andrea
Published: April 2021

Background

Multiple sclerosis (MS) is an inflammatory demyelinating disease with no known cure. Numerous diets are promoted to reduce symptoms or even cure MS, despite insufficient evidence for any therapeutic diet. There are few qualitative studies exploring the experiences of people with MS in relation to diet, and no use of theory to explain the findings.

Purpose

To explore the experiences of adults with MS when navigating dietary advice, their attitudes when making dietary decisions, and their needs regarding dietary resources and education.

Methods

In this qualitative study, we conducted six focus groups with people with MS (n = 33 plus one spouse without MS). Groups were audio‐recorded and transcribed verbatim. Primary analysis used a general inductive approach with thematic analysis. Secondary analysis aligned themes with the constructs of the self‐determination theory.

Results

Six themes emerged: (a) confusion about where to seek dietary advice; (b) scepticism towards national dietary guidelines; (c) personalized approaches to dietary change; (d) barriers to dietary changes; (e) judging if dietary changes work; and (f) wanting dietary guidelines for MS.

Conclusion

People with MS are highly motivated to make dietary changes and improve their health. The self‐determination theory explained why people with MS make dietary modifications, and the varying levels of motivation. MS‐specific dietary resources and nutrition education need to incorporate ways to increase autonomous forms of motivation. Future dietary intervention studies could use the self‐determination theory as a framework to improve long‐term adherence to healthier diets.
The role of EBV in haematolymphoid proliferations: emerging concepts relevant to diagnosis and treatment
Authors: Ababneh Emad , Saad Anas M , Crane Genevieve M
Published: April 2021

Epstein–Barr virus (EBV) is a ubiquitous gammaherpesvirus with >90% of the adult population worldwide harbouring latent infection. A small subset of those infected develop EBV‐associated neoplasms, including a range of lymphoproliferative disorders (LPD). The diagnostic distinction of these entities appears increasingly relevant as our understanding of EBV–host interactions and mechanisms of EBV‐driven lymphomagenesis improves. EBV may lower the mutational threshold for malignant transformation, create potential vulnerabilities related to viral alteration of cell metabolism and allow for improved immune targeting. However, these tumours may escape immune surveillance by affecting their immune microenvironment, limiting viral gene expression or potential loss of the viral episome. Methods to manipulate the latency state of the virus to enhance immunogenicity are emerging as well as the potential to detect so‐called ‘hit and run’ cases where EBV has been lost. Finally, measurement of EBV DNA remains an important biomarker for screening and monitoring of LPD. Methods to distinguish EBV DNA derived from virions during lytic activation from latent, methylated EBV DNA present in EBV‐associated neoplasms may broaden the utility of this testing, particularly in patients with compromised immune function. We highlight some of these emerging areas relevant to the diagnosis and treatment of EBV‐associated LPD with potential applicability to other EBV‐associated neoplasms.
Influence of variations in the environmental pH on the solubility and water sorption of a calcium silicate‐based root canal sealer
Authors: Silva E. J. N. L. , Ferreira C. M. , Pinto K. P. , Barbosa A. F. A. , Colaço M. V. , Sassone L. M.
Published: April 2021

Aim

To evaluate the influence of pH variation on the solubility and water sorption of a premixed calcium silicate‐based root canal sealer (EndoSequence BC Sealer) compared to the gold standard based on epoxy resin (AH Plus Jet) after immersion in distilled water and phosphate‐buffered saline (PBS).

Methodology

Solubility and water sorption were evaluated after immersion in distilled water or PBS at several pHs (5, 7 and 12) and the values were calculated as percentages of the original mass after 24 h, 7 and 30 days of immersion. The crystalline structures present in the sealers and surface precipitates were assessed by X‐ray diffraction. The Shapiro–Wilk’s test revealed that data were normally distributed; thus, statistical analysis was performed using one‐way anova and Tukey’s tests or independent t‐test, assuming a 5% α‐error.

Results

EndoSequence BC Sealer was associated with significantly greater water sorption and solubility compared to AH Plus Jet in all tested conditions (P < 0.05). The acid environment increased the 24 h solubility of EndoSequence BC Sealer immersed in PBS (P < 0.05) and did not induce significative changes in the water sorption (P > 0.05). Alkaline pH reduced the solubility of EndoSequence BC Sealer and increased that of AH Plus Jet at all experimental times and soaking media (P < 0.05). Alkaline environment also significantly increased the water sorption of AH Plus Jet immersed in PBS (P < 0.05). Immersion in PBS significantly reduced the solubility of EndoSequence BC Sealer and significantly increased that of AH Plus Jet (P < 0.05). Precipitates on the surface of EndoSequence BC Sealer corresponding to hydroxyapatite and calcium carbonate were detected after immersion in PBS at pH 5 and 7 for 30 days.

Conclusions

EndoSequence BC Sealer had significantly greater solubility and water sorption than AH Plus Jet. Although the alkaline pH and soaking media directly influenced the solubility and water sorption of the sealers, the solubility of AH Plus Jet remained within the limits recommended by ISO 6876, whilst the solubility of the EndoSequence BC Sealer did not comply with ISO recommendations in all the conditions tested.