bluuebunny/crossref_metadata_2025 huggingface dataset:
Young people and police making “Marginal Gains”: climbing fells, building relationships and changing police safeguarding practice
Authors: Factor Fiona Jane , Ackerley Elizabeth Lillian
Published: August 2019

Purpose

The purpose of this paper is to describe a youth work model of participatory research practice which utilises a range of methods within non-traditional research settings, highlighting the importance of trust, risk-taking and the creation of mutually respectful and non-hierarchical relationships. The paper suggests that such methods enable the development of new insights into previously intractable challenges when working with adolescents needing a safeguarding response from professionals.

Design/methodology/approach

The paper reflects on the challenges and successes of a project which brought police officers and young people together to develop solutions to improving safeguarding responses to young people affected by sexual violence and related forms of harm in adolescence. In particular, this paper focuses on a residential held in October 2016 in the Lake District involving 7 officers and 15 young people.

Findings

Despite a number of ethical challenges throughout the project, this paper makes the case that potentially high-risk participatory research projects can be supported and managed by university research centres. However, for these to be successful, staff need to work in trauma-informed ways, and possess high-level expertise in group work facilitation. Transparency, honesty, constancy and a range of different and creative activities, including mental and physical challenges, all contributed to the success of the project.

Originality/value

By detailing the empirical steps taken to develop, support and realise this project, this paper advances a youth work model of participatory research practice, filling an important gap within the methodological literature on participatory work with young people affected by sexual violence.
Brand personality and sexuality levels of luxury advertisements
Authors: Adomaitis Alyssa Dana , Saiki Diana
Published: August 2019

Purpose

The purpose of this paper is to determine the perceived personality of brands featuring different levels of sexuality in advertisements of luxury fashion brands.

Design/methodology/approach

To determine the identity of the company a “personality traits” scale by Geurenset al.(2015) was used with 25 brand personalities: conscientiousness/responsibility, extraversion/activity, emotional stability/emotionality, agreeableness/aggressiveness, and openness/simplicity. The final survey was then made available on Amazon Turk for two weeks. Each participant assessed one photograph at a level of sexuality given the gender they identified with the most.

Findings

There were 1,266 participants including 701 females and 565 females. Statistical analysis of the responses revealed that the degree of sexuality in the advertisements impacted brand perceptions. Among both genders, the greater degree of sexuality in the advertisement, the more the brand was considered less conscientious and responsible. The results also suggested that men and women view levels of sexuality differently. They varied most in the area of openness and simplicity, with men viewing advertisements of male models that had greater sexuality as simple. Men felt less sexuality was more emotional and romantic, while women viewed mid-level degree of sexuality in this manner.

Originality/value

Limited research has examined how level of sexuality influences perceived brand personality. The results contribute to theories pertaining to motivations to identify with a luxury fashion brand and provide strategies for luxury fashion brands to enhance their intended brand image.
Exploring current enablers and barriers for sustainable proximity manufacturing
Authors: Sirilertsuwan Petchprakai , Hjelmgren Daniel , Ekwall Daniel
Published: August 2019

Purpose

Amidst offshoring and reshoring trends, the purpose of this paper is to explore why business practitioners, especially from the labour-intensive clothing industry, choose to manufacture some products in proximity to the high-cost European market. Moreover, the rise of sustainability concerns led us to further explore whether these reasons relate to triple bottom line (TBL): business, environment and society.

Design/methodology/approach

The content analysis was adopted for within-case and cross-case analysis of data from semi-structured interviews of managers from 12 clothing companies.

Findings

Within-case analysis showed enablers and barriers (factors) of proximity manufacturing within each company’s characteristics under TBL. Cross-case analysis showed the most-mentioned enablers (high-quality suppliers, short lead-time and fast replenishment) and barriers (expensive production cost and lack of industrial set-up and seamstresses). The findings revealed both common and different factors from existing studies.

Research limitations/implications

Besides being motives for companies to bring manufacturing back to Europe, the results can be used by researchers and companies to develop criteria and performance measures of manufacturing locations for enhancing the TBL sustainability. Future research may explore different locations and industries for possibilities of proximity–manufacturing generalisation.

Social implications

Findings show that governments could focus on eliminating barriers of proximity manufacturing and creating favourable institutional infrastructure for the European clothing industry and sustainability.

Originality/value

This paper highlights updated proximity–manufacturing factors from practices in relation to TBL sustainability, including support for proximity manufacturing as a practice for TBL enhancement.
Sustainable supply chain management practices and performance
Authors: Baliga Ravindra , Raut Rakesh D. , Kamble Sachin S.
Published: August 2019

Purpose

Sustainable supply chain management (SSCM) is a relatively new sub-field of supply chain management (SCM). The performance of SSCM is based on the triple bottom line approach encompassing people-planet-profit, hence being defined not in only in social and environmental terms, but also the economic. The purpose of this paper is to develop an integrated study which uses antecedent-practices-performance principles in order to determine the drivers of SSCM practices, and the impact of these practices on sustainable supply chain performance. The importance of the study lies in the fact that the Indian Government is making significant efforts to boost the manufacturing sector, and sustainability is among the significant imperatives for Indian manufacturing to be competitive globally.

Design/methodology/approach

A conceptual model based on the antecedents-practices-performance principles was developed, and included six constructs identified from the literature: the drivers being the motivators of sustainability, lean management (LM) and supply management (SM), the practices were the environmental and social practices in the supply chain and, finally, the sustainable supply chain performance; eight hypotheses were conceived in the model development process. The survey instrument was conceptualised from an in-depth study of literature and was employed to conduct a survey of 211 operations and supply chain managers and functional heads from the Indian manufacturing industry. The scales were validated by employing the confirmatory factor analysis, followed by structural equation modelling to develop the structural relationships between the constructs using Amos 20.0.

Findings

The results of the SEM suggest that the antecedents, i.e. motivators, LM and SM, have a significant bearing on environmental and social practices in the SCM; these practices, in turn, also have a positive relationship with SSCM performance (except the relationship between LM and social practices in SCM) with acceptable goodness-of-fit measures. Thus out of the eight hypotheses, seven can be said to statistically significant.

Research limitations/implications

In addition to the motivators of sustainability, the study based on extant literature has considered LM and SM among the drivers of sustainability in SCM. The study has also identified that in earlier studies, the focus has been on environmental practices, and this integrated study has also included social practices in the supply chain.

Originality/value

This study suggests that sustainability performance may also be realised through lean and SM principles; an integrated perspective has been adopted with the consideration of both environmental and social practices. Further, the proposed model represents a novel integration of literature from diverse domains such as environmental management, business ethics and corporate social responsibility as well as performance management.
Edible film based on Vicia faba shell gum, nano silver and Helichrysum arenarium essence
Authors: Jahantigh Farzane
Published: August 2019

Purpose

The inclusion of natural antioxidants and nanoparticles into edible coatings can improve their structure, functionality and applicability in foods. This study aims to determine the antibacterial effect of new nano-composite based on bean pod shell gum (BPSG), silver nanoparticle (SNP) and herbal essential oil (EO).

Design/methodology/approach

For this purpose, BPSG (4 per cent w/v), SNP (0.5-1 per cent w/v) and Helichrysum arenarium EO (1-2 per cent v/v) were mixed. After preparation the edible film, the antibacterial activity was tested on five food-borne pathogenic bacteria in two categories including two-gram positives and three-gram negatives bacteria. The EO composition was determined by GC–mass spectrometry and the antibacterial activity was tested using disk diffusion test.

Findings

Results showed that gram-positive bacteria were more susceptible than gram-negative bacteria. Increasing Helichrysum arenarium EO and SNP content increased antimicrobial activity of the edible film based on BPSG, so that the treatment containing 2 per cent v/v Helichrysum arenarium EO and 1 per cent w/v SNP led to the highest inhibition zone (8.1-13.1 mm) compared to treatment containing 1 per cent v/v Helichrysum arenarium EO and 0.5 per cent w/v SNP with inhibition zone range of 5.4-9.9 mm and the difference was statistically significant (p = 0.41). Also, the chemical composition analysis of the EO identified a total of 38 compounds in which a-pinene (32 per cent), 1,8-cineole (16 per cent), α-humulene (15 per cent) and ß-caryophyllene (8 per cent) were the main fractions. Other separated components accounted less than 29 per cent of the oil.

Originality/value

In general, SNP and Helichrysum arenarium EO improved the functional properties including the antimicrobial activity of the edible film based on BPSG, which increases the potential to be used as active packaging for fresh products.
Plant trait‐based approaches to improve nitrogen cycling in agroecosystems
Authors: Abalos Diego , van Groenigen Jan Willem , Philippot Laurent , Lubbers Ingrid M. , De Deyn Gerlinde B.
Published: August 2019

Intensive agriculture is dominated by monocultures of high‐yielding plants that receive large applications of nitrogen (N) fertilizers to boost plant productivity. However, these systems have low N use efficiency (NUE) as fertilized plants generally take up less than half of the N applied. A large fraction of the remainder N is susceptible to be lost from the agroecosystem generating a cascade of environmental and socio‐economic problems. Climate change and projected global increases in fertilizer use pose further risks to N losses and yield stability.

We review and translate concepts from ecology in natural systems to demonstrate that NUE in intensive agroecosystems can be strongly increased by fine‐tuning the traits of the plant communities to the levels of N fertilization intensity.

We present key plant traits of importance for N‐cycling (architectural, morphological and physiological traits, as well as symbiotic associations and exudation patterns); discuss ecological (with soil fauna and N‐cycling microbial communities) and agronomic interactions of this approach; propose interdisciplinary methodologies for future research ranging from pot to global scales; and highlight possible solutions leading to an optimal balance between N fertilizer use and productivity.

Synthesis and applications. By showing the strong links between plant traits and nitrogen (N) cycling, our work opens possibilities to test ecologically informed hypotheses across gradients of soil fertility and N fertilizer management intensity, setting a research agenda for the coming years. Accordingly, the choice of plant species based on their functional traits will play a central role for the development of modern and productive agroecosystems that retain and use N more efficiently.
To what extent are bryophytes efficient dispersers?
Authors: Vanderpoorten Alain , Patiño Jairo , Désamoré Aurélie , Laenen Benjamin , Górski Piotr , Papp Beata , Holá Eva , Korpelainen Helena , Hardy Olivier
Published: August 2019

Bryophytes are typically seen as extremely efficient dispersers. Experimental evidence suggests that efficient short‐distance dispersal coupled with random long‐distance dispersal (LDD) leads to an inverse isolation effect. Under the latter, a higher genetic diversity of colonizing propagules is expected with increasing isolation, counteracting differentiation beyond the range of short‐distance dispersal.

This expectation is tested from a review of evidence on spatial genetic structure and analyses of isolation‐by‐distance (IBD) at different scales.

A decay of the IBD signal, characterized by non‐significant slopes between kinship coefficients and geographic distance was observed beyond 100 m. A second slope shift was observed at distances larger than 1 km, with a proportion of significant slopes in more than one third of the datasets.

The decay of the IBD signal beyond 100 m, which reflects efficient LDD, is consistent with the inverse isolation hypothesis. Persistence of a significant IBD signal at medium ranges in one third of the analysed cases suggests, however, that the inverse isolation effect is not a rule in bryophyte spore dispersal. Furthermore, the higher proportion of significant IBD patterns observed at scales over 100 km likely marks the limits of regional dispersal, beyond which an increasingly smaller proportion of spores travel.

Synthesis. We discuss the differences between experimental and genetic estimates of spore dispersal and conclude that geographic distance remains a significant proxy of spore colonization rates, with major consequences for our understanding of actual migration capacities in bryophytes, and hence, our capacity to model range shifts in a changing world.
Nitrogen alters effects of disturbance on annual grassland community diversity: Implications for restoration
Authors: Brandt Angela J. , Seabloom Eric W. , Cadotte Marc W.
Published: August 2019

In an era of anthropogenically altered disturbance regimes and increased nutrient loads, understanding how communities respond to these perturbations is essential for successful habitat restoration. Disturbance and resource supply can affect community diversity by altering community assembly processes, such as recruitment, mortality or competitive inequalities. The mechanisms behind community responses to these drivers will differentially affect multiple facets of diversity.

Here we examine how factorial manipulations of disturbance (raking to remove above‐ground vegetation) and nitrogen supply affect taxonomic and phylogenetic diversity of predominantly annual California grassland communities spanning a 500‐km latitudinal and twofold rainfall gradient. The disturbance caused density‐independent biomass removal and increased access to resources such as space and light, thus mimicking demographic effects of disturbance as considered in ecological models and broadly applicable to empirical systems. We used paired metrics of richness, evenness and community composition to compare evidence from taxonomy and phylogeny.

Disturbance increased species and phylogenetic diversity (richness and evenness metrics). However, nitrogen addition interacted with disturbance to reduce species richness and phylogenetic diversity. Undisturbed communities were more strongly clustered phylogenetically, but disturbance eroded this clustering such that communities became more random (i.e. indistinguishable from a null model of assembly). Species composition differed between disturbed and undisturbed communities, and many species were observed in only one community type. Disturbance interacted with nitrogen supply to alter phylogenetic composition of communities, and recently disturbed communities were more spatially variable in phylogenetic composition than undisturbed communities. Phylogenetic composition of communities also differed among nitrogen treatments.

Synthesis. Our results suggest that disturbing these grassland communities by removing above‐ground vegetation increased community diversity by increasing recruitment. Seed addition following this type of disturbance is thus likely to be an effective restoration technique. However, we have shown that disturbance combined with nitrogen enrichment reduces community diversity. The mechanism for this enrichment effect does not appear to be linked to increased productivity leading to light limitation. This work suggests restoration efforts employing biomass removal must take nutrient availability into account to maximize local community diversity.
Trait hierarchies and intraspecific variability drive competitive interactions in Mediterranean annual plants
Authors: Carmona Carlos P. , de Bello Francesco , Azcárate Francisco M. , Mason Norman W. H. , Peco Begoña
Published: August 2019

Both intra‐ and interspecific differences in traits may modulate interactions between plants. Two mechanisms are hypothesized to regulate these effects: competitive hierarchies and trait dissimilarities, but it is unclear how the prevalence of each might depend on environmental conditions and on intra and interspecific differences.

We sowed six replicates of all possible pairwise combinations across eight annual species (including conspecific competition and individuals without competitors), in pots under two levels of fertilization. We measured above‐ and below‐ground traits and total biomass of the focal individuals. We expressed competition as the decrease in biomass of focal individuals relative to biomass without competition, and modelled competition using directional (hierarchy) or non‐directional (dissimilarity) trait differences, with or without intraspecific variability (ITV).

We found evidence of different trait hierarchies operating under different fertilization conditions but little support for trait dissimilarities. The negative effect of competition on focal plants increased with the height of the competitors in both of fertilization levels. Further, in unfertilized conditions, plants with lower specific leaf area (SLA) and larger root systems experienced less competition. Including ITV in trait hierarchies substantially improved our ability to predict the intensity of competition. This was partly due to ITV reducing competitive hierarchies.

Synthesis. Our results underscore the importance of traits in driving interactions among plants. Competitive relationships between species depend on complex interactions between trait intra and interspecific differences and resource availability. ITV appears to be a mechanism capable of reducing trait hierarchies, and hence the intensity of competition between coexisting plants.
Hedonic Price of Housing Space
Authors: Agarwal Sumit , Chen Yanying , Li Jing , Tan Yi Jin
Published: August 2019

This article estimates hedonic prices for different levels of housing space, by exploiting a unique space‐adding project in Singapore that added a uniform amount of space to each existing housing unit regardless of the original size. This space adding program was carried out if sufficient residents vote in favor of space adding. Using a difference‐in‐differences (DiD) strategy after restricting our sample to narrow margins around the voting cutoff, we find that the additional space increased the resale price of a housing unit by 7% on average, and the extent of price appreciation varied significantly across the original size of the units.
Mental Effects of Excess Parathyroid Hormone in Hemodialysis Patients: A Possible Role for Parathyroid 2 Hormone Receptor?
Authors: Diskin James , Diskin Charles J
Published: August 2019

Depression as measured by the kidney disease quality of life (KDQOL) form is known to be an independent risk factor for mortality dialysis patients. Excess parathyroid hormone (PTH) has long been associated with neuropsychiatric disturbances. Those psychiatric complications are currently attributed to hypercalcemia with very little evidence; however, with the discovery of the parathyroid hormone 2 receptor (PTH2R) in the brain which can be activated by PTH, PTH2R might indicate a direct effect of PTH. As secondary and tertiary hyperparathyroidism is common in dialysis patients where the serum calcium is low or normal, we chose to investigate a possible relationship between PTH levels and depression in dialysis patients. This was a matched pair observational study with 10 patients with intact PTH values above 1000 pg/mL who were matched with 10 patients who had PTH values less than 400 pg/mL for the presence of diabetes, years on dialysis, duration of dialysis time, Kt/V, hemoglobin, and 25 OH vitamin D levels, as well as intravenous iron and erythropoietin administration. The Kidney Disease Quality of Life questionnaire (KDQOL‐36) scores and patient Health Questionnaire scores were analyzed during that time. All variables underwent tests for normality and matched pair t‐test. All subscales of the KDQOL‐36 were worse in the high PTH group with the effect on daily life reaching P = 0.01 and the burden of disease and symptoms both reaching P = 0.02. PTH and PTH2R may be appropriate targets for investigations to improve the quality of life in hemodialysis patients.
Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016
Authors: Garbutcheon‐Singh Kieran B. , Curchin David J. , McCormack Christopher J. , Smith Saxon D.
Published: August 2019

Background/Objectives

Merkel cell carcinoma (MCC) is a highly invasive cutaneous malignancy. The objective of this study was to investigate the incidence and trends of MCC in Victoria, Australia, between 1986 and 2016.

Methods

Population‐based, descriptive analysis of Victorian Cancer Registry (VCR) data. The de‐identified records of patients with MCC were obtained from Victoria residents diagnosed between 1986 and 2016. Trends in age‐standardised incidences were examined using joinpoint analysis.

Results

A total of 1095 cases were found. Incidence of MCC was 3.9 per 100 000 for men and 1.5 per 100 000 for women. The incidence of MCC in men 66–85 is increasing at an annual rate of 4.2% (2.8–5.8%, 95% CI). However, since 2002 the incidence in women in the same age group has been decreasing. Whilst there is an overall stabilisation in the incidence of MCC, incidence of MCC for males is increasing. For MCC in males 85 years old and over, the incidence of MCC was 26.8 per 100 000 between 2012 and 2016. Relative 5‐year survival for patients diagnosed between 2008 and 2012 is 50%.

Conclusion

Merkel cell carcinoma remains an aggressive cancer, especially among older men. Differences in trends seen in local data can help target preventative and early intervention management strategies in specific groups.
Upregulation of IL‐36 cytokines in folliculitis and eosinophilic pustular folliculitis
Authors: Sato Seisho , Chiba Takahito , Nakahara Takeshi , Furue Masutaka
Published: August 2019

Background

Members of the interleukin (IL)‐36 family, IL‐36α, IL‐36β and IL‐36γ, are potent chemoattractive cytokines for neutrophils and eosinophils. IL‐36 receptor antagonist (IL‐36Ra) inhibits IL‐36α, IL‐36β and IL‐36γ activity. However, the immunohistological expression of IL‐36α, IL‐36β, IL‐36γ and IL‐36Ra has never been addressed in normal follicles, folliculitis or eosinophilic pustular folliculitis (EPF).

Methods

We performed immunohistochemical staining for IL‐36α, IL‐36β, IL‐36γ and IL‐36Ra using 10 cases of EPF, nine of non‐specific folliculitis, 10 normal skin samples and 10 samples of normal follicles adjacent to a sebaceous naevus as a control. Two dermatologists, who were blind to the patient records, evaluated all of the slides.

Results

The immunoreactive IL‐36α was hardly detected in the follicular epithelium and epidermis in the normal skin, folliculitis or EPF. The expression of IL‐36β, IL‐36γ and IL‐36Ra was augmented in both folliculitis and EPF compared with that in normal follicles. Negative correlations were detected between IL‐36β and IL‐36Ra and between IL‐36γ and IL‐36Ra in normal follicles; however, these were absent in folliculitis. In contrast to normal follicles and folliculitis, a significant positive correlation between IL‐36β/γ and IL‐36Ra was shown in EPF.

Conclusions

The overexpression of IL‐36β, IL‐36γ and IL‐36Ra is an integral part of the inflammatory response of folliculitis and EPF. The coordinated expression of IL‐36γ and IL‐36Ra may be related to the pathomechanism of EPF.
Taming the Ontological Wolves: Learning from Iroquoian Effigy Objects
Authors: Cipolla Craig N.
Published: August 2019

Currently on the rise in archaeology, ontological approaches promise new ways of engaging with alterity of various kinds—different people, different times, different forms, even different worlds. This work promises to aid in critical reflections on the arbitrary nature of the Western gaze and to recognize and incorporate non‐Western knowledge in new manners. There are, however, several challenges to address. First, as noted by several leading thinkers in this area, the present range of ontological approaches include contrasting theoretical underpinnings. Second, these approaches are rarely considered in relation to the practical challenges of specific archaeological cases, particularly contexts of settler colonialism in which practitioners are attuned to the potential colonial nature of their work. I divide ontologically engaged archaeologies into three related but distinct groups and use a small museum assemblage of seventeenth‐century Wendat materials from Ontario to help think through these three theories. In comparing approaches, I outline their respective strengths, weaknesses, and points in need of further clarification. I conclude that the ontological turns offer new and valuable angles of articulation with archaeological materials but that archaeologists must adopt them cautiously if they are to avoid repeating or continuing some of the darkest parts of our (colonial) disciplinary history. [ontology, archaeology, new materialism, archaeological theory, effigies, colonialism, Iroquoian archaeology, Ontario]
Delivery room skin‐to‐skin contact for preterm infants—A randomized clinical trial
Authors: Mehler Katrin , Hucklenbruch‐Rother Eva , Trautmann‐Villalba Patricia , Becker Ingrid , Roth Bernhard , Kribs Angela
Published: August 2019

Aim

To investigate the effects of 60 minutes delivery room skin‐to‐skin contact (DR‐SSC) compared with 5 minutes visual contact (VC) on mother‐child interaction (MCI), salivary cortisol, maternal depression, stress and bonding at 6 months corrected age.

Methods

A single‐centre randomized controlled trial conducted in a German level III NICU. Eighty‐eight preterm infants (25‐32 weeks of gestational age) were randomized after initial stabilization to either 60 minutes DR‐SSC or 5 minutes VC. Forty‐five infants were allocated to DR‐SSC, 43 to VC.

Results

Delivery room skin‐to‐skin contact dyads showed a higher quantity of maternal motoric (18 vs 15, P = .030), infant's vocal (7 vs 5, P = .044) and motoric (20 vs 15, P = .032) responses. Moreover, the combined score of maternal and infant responsive behaviour was higher (86 vs 71, P = .041) in DR‐SSC dyads. DR‐SSC mothers had lower risk of both, early postpartum depression (15% vs 45%, P = .003) and impaired bonding (Score 3 vs 5, P = .031).

Conclusion

In addition to regular intermittent kangaroo mother care, DR‐SSC promotes MCI and decreases risk of maternal depression and bonding problems. Thus, DR‐SSC may have positive effects on preterm development.
Effects of the ventilatory stimulant, doxapram on human TASK‐3 (KCNK9, K2P9.1) channels and TASK‐1 (KCNK3, K2P3.1) channels
Authors: Cunningham Kevin P. , MacIntyre D. Euan , Mathie Alistair , Veale Emma L.
Published: August 2019

Aims

The mode of action by which doxapram acts as a respiratory stimulant in humans is controversial. Studies in rodent models, have shown that doxapram is a more potent and selective inhibitor of TASK‐1 and TASK‐1/TASK‐3 heterodimer channels, than TASK‐3. Here we investigate the direct effect of doxapram and chirally separated, individual positive and negative enantiomers of the compound, on both human and mouse, homodimeric and heterodimeric variants of TASK‐1 and TASK‐3.

Methods

Whole‐cell patch clamp electrophysiology on tsA201 cells was used to assess the potency of doxapram on cloned human or mouse TASK‐1, TASK‐3 and TASK‐2 channels. Mutations of amino acids in the pore‐lining region of TASK‐3 channels were introduced using site‐directed mutagenesis.

Results

Doxapram was an equipotent inhibitor of human TASK‐1 and TASK‐3 channels, compared with mouse channel variants, where it was more selective for TASK‐1 and heterodimers of TASK‐1 and TASK‐3. The effect of doxapram could be attenuated by either the removal of the C‐terminus of human TASK‐3 channels or mutations of particular hydrophobic residues in the pore‐lining region. These mutations, however, did not alter the effect of a known extracellular inhibitor of TASK‐3, zinc. The positive enantiomer of doxapram, GAL‐054, was a more potent antagonist of TASK channels, than doxapram, whereas the negative enantiomer, GAL‐053, had little inhibitory effect.

Conclusion

These data show that in contrast to rodent channels, doxapram is a potent inhibitor of both TASK‐1 and TASK‐3 human channels, providing further understanding of the pharmacological profile of doxapram in humans and informing the development of new therapeutic agents.
Increased risk of thiopurine‐related adverse events in elderly patients with IBD
Authors: Calafat Margalida , Mañosa Míriam , Cañete Fiorella , Ricart Elena , Iglesias Eva , Calvo Marta , Rodríguez‐Moranta Francisco , Taxonera Carlos , Nos Pilar , Mesonero Francisco , Martín‐Arranz María-Dolores , Mínguez Miguel , Gisbert Javier P. , García‐López Santiago , de Francisco Ruth , Gomollón Fernando , Calvet Xavier , Garcia‐Planella Esther , Rivero Montserrat , Martínez‐Cadilla Jesús , Argüelles Federico , Arias Lara , Cimavilla Marta , Zabana Yamile , Domènech Eugeni ,   the ENEIDA registry of GETECCU
Published: August 2019

Background

Thiopurines are the most widely used immunosuppressants in IBD although drug‐related adverse events (AE) occur in 20%‐30% of cases.

Aim

To evaluate the safety of thiopurines in elderly IBD patients

Methods

Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine‐related AEs registered in the ENEIDA database were compared.

Results

Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2‐55] vs 32 [IQR 5‐82] months; P < .001). Patients starting >60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs.

Conclusion

In elderly IBD patients, thiopurines are associated with an increased risk of non‐infectious, non‐neoplastic, AEs.
Beyond market, firm, and state: Mapping the ethics of global value chains
Authors: Singer Abraham A. , van der Ven Hamish
Published: August 2019

The growth of global value chains (GVCs) and the emergence of novel forms of value chain governance pose two questions for normative business ethics. First, how should we conceptualize the relationships between members of a GVC? Second, what ethical implications follow from these relationships, both with respect to interactions between GVC members and with respect to achieving broader transnational governance goals? We address these questions by examining the emergence of transnational eco‐labeling as an increasingly prominent form of GVC governance that is redefining the relationship between nominally independent firms. On the first question, we argue that GVCs occupy a middle ground between intrafirm and interfirm transactions, thereby posing a challenge to theoretical frameworks that attempt to apply ethical standards based on transaction types. On the second question, we argue that this unique institutional status leads to a range of novel ethical considerations and dilemmas for GVC members. Lead firms, their suppliers, and third‐party standard‐setters all confront new ethical quandaries when third‐party eco‐labeling is introduced to a GVC. The nature of these quandaries means that, while GVCs may be well‐positioned to serve as instruments of transnational governance, they are frequently not well‐oriented to do so. Our analysis marks an initial attempt to map the ethical considerations that apply to members of a GVC, and in doing so, places the literature on normative business ethics and transnational governance in a closer conversation.
Structured gene‐environment interaction analysis
Authors: Wu Mengyun , Zhang Qingzhao , Ma Shuangge
Published: August 2019

For the etiology, progression, and treatment of complex diseases, gene‐environment (G‐E) interactions have important implications beyond the main G and E effects. G‐E interaction analysis can be more challenging with higher dimensionality and need for accommodating the “main effects, interactions” hierarchy. In recent literature, an array of novel methods, many of which are based on the penalization technique, have been developed. In most of these studies, however, the structures of G measurements, for example, the adjacency structure of single nucleotide polymorphisms (SNPs; attributable to their physical adjacency on the chromosomes) and the network structure of gene expressions (attributable to their coordinated biological functions and correlated measurements) have not been well accommodated. In this study, we develop structured G‐E interaction analysis, where such structures are accommodated using penalization for both the main G effects and interactions. Penalization is also applied for regularized estimation and selection. The proposed structured interaction analysis can be effectively realized. It is shown to have consistency properties under high‐dimensional settings. Simulations and analysis of GENEVA diabetes data with SNP measurements and TCGA melanoma data with gene expression measurements demonstrate its competitive practical performance.
JAK1/2 pathway inhibition suppresses M2 polarization and overcomes resistance of myeloma to lenalidomide by reducing TRIB1, MUC1, CD44, CXCL12, and CXCR4 expression
Authors: Chen Haiming , Li Mingjie , Sanchez Eric , Soof Camilia M. , Bujarski Sean , Ng Nicole , Cao Jasmin , Hekmati Tara , Zahab Brian , Nosrati Jason D. , Wen Mingxiang , Wang Cathy S. , Tang George , Xu Ning , Spektor Tanya M. , Berenson James R.
Published: August 2019

Monocytes polarize into pro‐inflammatory macrophage‐1 (M1) or alternative macrophage‐2 (M2) states with distinct phenotypes and physiological functions. M2 cells promote tumour growth and metastasis whereas M1 macrophages show anti‐tumour effects. We found that M2 cells were increased whereas M1 cells were decreased in bone marrow (BM) from multiple myeloma (MM) patients with progressive disease (PD) compared to those in complete remission (CR). Gene expression of Tribbles homolog 1 (TRIB1) protein kinase, an inducer of M2 polarization, was increased in BM from MM patients with PD compared to those in CR. Ruxolitinib (RUX) is an inhibitor of the Janus kinase family of protein tyrosine kinases (JAKs) and is effective for treating patients with myeloproliferative disorders. RUX markedly reduces both M2 polarization and TRIB1 gene expression in MM both in vitro and in vivo in human MM xenografts in severe combined immunodeficient mice. RUX also downregulates the expression of CXCL12, CXCR4, MUC1, and CD44 in MM cells and monocytes co‐cultured with MM tumour cells; overexpression of these genes is associated with resistance of MM cells to the immunomodulatory agent lenalidomide. These results provide the rationale for evaluation of JAK inhibitors, including MM BM in combination with lenalidomide, for the treatment of MM patients.
Supporting positive sexual health for persons with developmental disabilities: Stories about the right to love
Authors: Sitter Kathleen C. , Burke Amy C. , Ladhani Sheliza , Mallay Nicole
Published: August 2019

Accessible Summary

This research is about the sexual rights of persons with developmental disabilities.

For 12 months, nine adults with developmental disabilities and three allies created videos about love and intimacy.

The group found that family members, caregivers and support workers can make it hard for people with developmental disabilities to learn about and experience healthy relationships.

This research is important because it promotes the experiences and perspectives of persons with developmental disabilities, which can hopefully lead to positive changes in attitudes and service delivery that support positive sexual health.

Background

Although sexual rights are human rights, persons with developmental disabilities are often excluded from developing positive sexual health due to societal attitudes, stigma, a lack of education and limited opportunities.

Methods

As a part of a 12‐month participatory action research study in a western Canadian province, nine adults with developmental disabilities and three allies created videos that explored the dimensions of sexual health as experienced by people with developmental disabilities. Participants were involved in all stages of the filming process. The filming topics identified by the participants emerged as the core research themes.

Results

Persons with developmental disabilities often have limited opportunities to develop and nurture intimate relationships. Participants also identified that: (a) a lack of support from caregivers, (b) a lack of education about sexual health, (c) ableist spaces and (d) the absence of agency policies that acknowledge and protect sexual rights create further obstacles.

Conclusions

Inclusive practices where the sexual rights of persons with developmental disabilities are respected and celebrated are critical in promoting positive sexual health. For many agencies, this requires reframing policies and programmes that include acknowledging and protecting the sexual rights of persons with developmental disabilities. While providing accessible pedagogical opportunities about sexual health was identified as important, ensuring curriculum delivery for support workers, as well as educating families and caregivers about the importance of sexual health and inclusion, is paramount, where the views and opinions of persons with developmental disabilities are at the forefront of the process.
Memory and standing balance after multisensory stimulation in a Snoezelen room in people with moderate learning disabilities
Authors: Toro Brigitte
Published: August 2019

Accessible Summary

Multisensory stimulation improves attention, which can also improve memory and standing balance of people with learning disabilities, even at a high age.

Improved standing balance and body awareness may help reduce falls in people with moderate learning disabilities.

Therapeutic treatments could be more effective if preceded by multisensory stimulation.

Background

The Snoezelen room provides a multisensory environment for people with learning disabilities.

Method

Thirty‐five residents were recruited from a convenience sample of people living in a residential centre. A repeated‐measures, within‐subject design was used to evaluate the participants during three conditions: a) Snoezelen room, b) control period and c) watching television. The outcome measures were digit span memory tests and Romberg balance tests. One‐way repeated‐measures ANOVAs and paired‐samples t tests were performed on the data.

Results

ANOVA results show that there was a significant effect over time in the amount of digits remembered and in balancing ability between the three conditions (p < .0005). T tests confirmed that the Snoezelen condition was responsible for the significant improvements in memory and balancing ability.

Conclusion

Participants performed significantly better with memory tasks and balancing skills after having attended multisensory stimulation in a Snoezelen room. This may be due to improved mindfulness, which is correlated with improvements of concentration, learning ability and motor skills caused by neurophysiologic changes of the brain.
Holocene sedimentary and environmental development of Aarhus Bay, Denmark – a multi‐proxy study
Authors: Rasmussen Peter , Pantopoulos George , Jensen Jørn B. , Olsen Jesper , Røy Hans , Bennike Ole
Published: August 2019

Holocene sedimentation patterns and environmental development in Aarhus Bay, Denmark, were reconstructed based on proxy analyses of two sediment cores (M1 and M5). Together, the two cores offer an opportunity to examine the history of the area during the past c. 10 000 years. The investigation consisted of acoustic mapping and multi‐proxy analyses of the sediment cores including macrofossils, sediment physical properties, sediment accumulation rates, grain size, and X‐ray fluorescence elemental counts. Radiocarbon dating of the two sediment successions revealed that they cover the periods c. 10 000–3700 cal. a BP (M1) and c. 4400 cal. a BP to the present (M5). The data from the M1 site indicate the presence of a near‐shore lake environment between c. 10 000 and 9000 cal. a BP. The first intrusion of marine water into the area is dated to c. 9000 cal. a BP. In the following c. 1300 years, brackish‐water conditions prevailed in the area characterized by a mixture of taxa from marine, limnic and terrestrial habitats, reflecting a shallow estuarine environment. Around 7700 cal. a BP full marine conditions were established, accompanied by a marked increase in sedimentation rates. The changes to full marine conditions and higher sedimentation rates are probably due to a significant sea‐level rise leading to flooding of former land areas and intensified erosion. A subsequent distinct decrease in sedimentation rates around 6350 cal. a BP is presumably linked to a previously documented sea‐level drop about this time. Continuous sedimentation ceased around 3700 cal. a BP in the central part of the bay, most probably due to a major sea‐level lowering involving widespread erosion. In the eastern and deeper part of the bay, sedimentation continued until today. Fully marine conditions prevailed there for at least the last 4400 years.
Mind the gap (junction): cGMP induced by nitric oxide in cardiac myocytes originates from cardiac fibroblasts
Authors: Menges Lukas , Krawutschke Christian , Füchtbauer Ernst‐Martin , Füchtbauer Annette , Sandner Peter , Koesling Doris , Russwurm Michael
Published: August 2019

Background and Purpose

The intracellular signalling molecule cGMP, formed by NO‐sensitive GC (NO–GC), has an established function in the vascular system. Despite numerous reports about NO‐induced cGMP effects in the heart, the underlying cGMP signals are poorly characterized.

Experimental Approach

Therefore, we analysed cGMP signals in cardiac myocytes and fibroblasts isolated from knock‐in mice expressing a FRET‐based cGMP indicator.

Key Results

Whereas in cardiac myocytes, none of the known NO–GC‐activating substances (NO, GC activators, and GC stimulators) increased cGMP even in the presence of PDE inhibitors, they induced substantial cGMP increases in cardiac fibroblasts. As cardiac myocytes and fibroblasts are electrically connected via gap junctions, we asked whether cGMP can take the same route. Indeed, in cardiomyocytes co‐cultured on cardiac fibroblasts, NO‐induced cGMP signals were detectable, and two groups of unrelated gap junction inhibitors abolished these signals.

Conclusion and Implication

We conclude that NO‐induced cGMP formed in cardiac fibroblasts enters cardiac myocytes via gap junctions thereby turning cGMP into an intercellular signalling molecule. The findings shed new light on NO/cGMP signalling in the heart and will potentially broaden therapeutic opportunities for cardiac disease.
Trichostatin A blocks aldosterone‐induced Na+ transport and control of serum‐ and glucocorticoid‐inducible kinase 1 in cortical collecting duct cells
Authors: Mansley Morag K. , Roe Andrew J. , Francis Sarah L. , Gill Jason H. , Bailey Matthew A. , Wilson Stuart M.
Published: August 2019

Background and Purpose

Aldosterone stimulates epithelial Na+ channel (ENaC)‐dependent Na+ retention in the cortical collecting duct (CCD) of the kidney by activating mineralocorticoid receptors that promote expression of serum and glucocorticoid‐inducible kinase 1 (SGK1). This response is critical to BP homeostasis. It has previously been suggested that inhibiting lysine deacetylases (KDACs) can post‐transcriptionally disrupt this response by promoting acetylation of the mineralocorticoid receptor. The present study critically evaluates this hypothesis.

Experimental Approach

Electrometric and molecular methods were used to define the effects of a pan‐KDAC inhibitor, trichostatin A, on the responses to a physiologically relevant concentration of aldosterone (3 nM) in murine mCCDcl1 cells.

Key Results

Aldosterone augmented ENaC‐induced Na+ absorption and increased SGK1 activity and abundance, as expected. In the presence of trichostatin A, these responses were suppressed. Trichostatin A‐induced inhibition of KDAC was confirmed by increased acetylation of histone H3, H4, and α‐tubulin. Trichostatin A did not block the electrometric response to insulin, a hormone that activates SGK1 independently of increased transcription, indicating that trichostatin A has no direct effect upon the SGK1/ENaC pathway.

Conclusions and Implications

Inhibition of lysine de‐acetylation suppresses aldosterone‐dependent control over the SGK1–ENaC pathway but does not perturb post‐transcriptional signalling, providing a physiological basis for the anti‐hypertensive action of KDAC inhibition seen in vivo.