bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of founder’s regulatory focus on the process of firm birth and firm abandonment
Authors: Koumbarakis Paris , Bergmann Heiko , Volery Thierry
Published: October 2020

Purpose

The purpose of this paper is to show how self-regulation influences the relationship between nascent entrepreneurial exploitation activities, firm birth and firm abandonment.

Design/methodology/approach

This study draws from a unique longitudinal dataset of 181 nascent entrepreneurs from Switzerland who have been interviewed by phone in 2015 and 2016. It uses a moderated binary logistic regression to test the hypotheses.

Findings

This study provides evidence that discrepancies in promotion orientation can explain different ways exploitation can lead to an increased likelihood of firm birth and a decreased likelihood of firm abandonment while respectively increasing persistence. Findings suggest that this is attributed to the regulatory fit between a promotion orientation and exploitation activities.

Research limitations/implications

For scholars, our findings provide insights into reasons for entrepreneurial persistence, as well as how firm birth can be achieved with different levels of exploitation activities.

Practical implications

This study provides entrepreneurs with information on how to increase their persistence as well as the likelihood of firm birth while considering their regulatory focus.

Originality/value

Based on regulatory focus theory, this paper highlights different paths to firm birth with varying quantity of exploitation activities. We contribute to a greater understanding of firm emergence by accounting for the impact of regulatory foci.
The interaction effect of transactional-transformational leadership on employee commitment in a developing country
Authors: Puni Albert , Hilton Sam Kris , Quao Benedicta
Published: October 2020

Purpose

While substantial a number of research studies have examined the effect of leadership styles on work-related behaviour, the interaction effect of transactional-transformational leadership on work-related behaviour has been rarely investigated in a developing context. Thus, this study aims to examine the interaction effect of transactional-transformational leadership on employee commitment in Ghana.

Design/methodology/approach

The study used descriptive and cross-sectional survey designs. Cross-sectional data was obtained from 360 employees in the aviation industry of Ghana and analyzed using descriptive statistics, correlation and hierarchical regression techniques.

Findings

Transactional leadership style has a significant positive effect on employee commitment. However, when transformational leadership was added on transactional leadership base, there was no augmentation effect of transformational leadership style in predicting employee commitment. The results further indicate that there was a negative interaction effect of transactional and transformational leadership styles on employee commitment.

Practical implications

The findings imply that organizational leaders can improve employee commitment by purely resorting to transactional leadership behaviours. Leaders can also enhance employee commitment by augmenting transactional leadership behaviours on transformational leadership, as the reverse has no augmentation effect.

Originality/value

This study considerably complements existing leadership literature by establishing how a transformational leadership style can augment and/or interact with transaction leadership style to influence employee commitment in a developing country.
Attitude toward social media reviews and restaurant visit intention: a Bangladeshi perspective
Authors: Popy Nurun Naher , Bappy Tauhid Ahmed
Published: October 2020

Purpose

While the usage of social media reviews has become increasingly popular in recent years, few studies in this context of Bangladesh have investigated its impact on restaurant visit intention. Therefore, this study aims to explain the role of attitude toward social media reviews in customers' restaurant visit intention from the perspective of Bangladesh. In doing so, predictors of attitude toward social media reviews were also ascertained and their indirect effects on restaurant visit intention were investigated.

Design/methodology/approach

A survey questionnaire was administered to 300 university students. A six-factor based measurement model was proposed, and structural equation modeling (SEM) was used in testing the hypotheses represented by the model. Furthermore, a focus group discussion with 12 respondents was also held to assess how negative reviews on social media affect the customers' restaurant visit intention.

Findings

This study reveals that perceived usefulness, perceived ease of use, trustworthiness and information quality of social media reviews are positively related to attitude toward using positive social media reviews for choosing a restaurant. Furthermore, attitude toward positive social media reviews directly contributes to the intention to visit restaurants. Besides, attitude toward social media reviews fully mediates the relationship of perceived usefulness, perceived ease of use and trustworthiness with restaurant visit intention, whereas it partially mediates the relationship between information quality and restaurant visit intention. Besides, results from focus group discussion revealed that customers typically trust negative reviews which reduce their intent to visit restaurants.

Research limitations/implications

The samples chosen for this study belong only to a particular stratum of the population (students from a specific institution/university). Hence, the outcomes should be generalized with caution.

Practical implications

This study provides practical guidelines for the restaurant marketers to formulate improved strategic decisions by tracking the restaurant customers' attitudes, behavioral intentions, sentiments and share of voice on social media platforms. The results of this study will encourage the restaurant marketers to build sustainable relationships with influential food bloggers to spawn positive electronic word of mouth (e-WOM).

Originality/value

This is one of the first studies in Bangladesh that have covered up a timely and untouched research area, providing empirical evidence regarding the effects of attitude toward social media reviews on restaurant visit intent in the context of a South Asian country like Bangladesh.
Individual variation in seasonal acclimation by sympatric amphibians: A climate change perspective
Authors: Winterová Barbora , Gvoždík Lumír
Published: October 2020

Many ectotherms modify their phenotype seasonally as a response to variation in abiotic factors. Given the potential of seasonal acclimation to reduce the impact of climate change on the dynamics of ectotherm populations, the adaptive evolution of this reversible plasticity has received much attention. Nevertheless, the key assumption of selection on the magnitude of seasonal acclimation, consistent among‐individual variation (repeatability), remains unexplored.

We studied the short‐ (across body temperatures) and long‐term (over two consecutive years) repeatability of seasonal acclimation on standard metabolic rate (SMR) and spontaneous locomotor activity (SLA) in two sympatric newt taxa, Ichthyosaura alpestris and Lissotriton vulgaris. We exposed the newts to various fluctuating thermal regimes over spring and summer and measured SMR and SLA at three body temperatures in each individual over two consecutive years. We quantified seasonal acclimation as difference between summer and spring trait values.

We show that individuals of both species vary substantially in their seasonal acclimation responses. Body temperature affected the population means of seasonal acclimation in a quadratic I. alpestris or linear L. vulgaris fashion. Both short‐ and long‐term repeatability of SMR and SLA seasonal acclimation were poor and both species varied in the amount of total variation in the plastic response. Seasonal shifts in environmental temperatures showed high variation between years, but with no apparent trend attributable to local climate change.

Our results demonstrate that seasonal SMR and SLA acclimation prevents the establishment of a consistent relationship between individual trait values and environmental gradients, which may limit the adaptive evolution of this plastic response. Disparate thermal dependence patterns and the amount of total variation in seasonal acclimation suggest a species‐specific ability for coping with stochasticity of seasonal variation in the thermal environment.

To sum up, information on individual variation and population means measured across ecologically realistic body temperatures is necessary to fully understand the occurrence of seasonal acclimation across taxa and its role in the adaptive capacity to climate change.

A free Plain Language Summary can be found within the Supporting Information of this article.
Differential effects of fertilisers on pollination and parasitoid interaction networks
Authors: Villa‐Galaviz Edith , Smart Simon M. , Clare Elizabeth L. , Ward Susan E. , Memmott Jane
Published: October 2020

Grassland fertilisation drives non‐random plant loss resulting in areas dominated by perennial grass species. How these changes cascade through linked trophic levels, however, is not well understood.

We studied how grassland fertilisation propagates change through the plant assemblage into the plant–flower‐visitor, plant–leaf miner and leaf miner–parasitoid networks using a year's data collection from a long‐term grassland fertiliser application experiment. Our experiment had three fertiliser treatments each applied to replicate plots 15 m2 in size: mineral fertiliser, farmyard manure, and mineral fertiliser and farmyard manure combined, along with a control of no fertiliser.

The combined treatment had the most significant impact, and both plant species richness and floral abundance decreased with the addition of fertiliser. While insect species richness was unaffected by fertiliser treatment, fertilised plots had a significantly higher abundance of leaf miners and parasitoids and a significantly lower abundance of bumblebees. The plant–flower‐visitor and plant–herbivore networks showed higher values of vulnerability and lower modularity with fertiliser addition, while leaf miner–parasitoid networks showed a rise in generality.

The different groups of insects were impacted by fertilisers to varying degrees: while the effect on abundance was the highest for leaf miners, the vulnerability and modularity of flower‐visitor networks was the most affected. The impact on the abundance of leaf miners was positive and three times higher than the impact on parasitoids, and the impact on bumblebee abundance was negative and double the magnitude of impact on flower abundance.

Overall, our results show that while insect species richness was unaffected by fertilisers, network structure changed significantly as the replacement of forbs by grasses resulted in changes in relative abundance across trophic levels, with the direction of change depending on the type of network.

Synthesis. By studying multiple networks simultaneously, we were able to rank the relative impact of habitat change on the different groups of species within the community. This provided a more holistic picture of the impact of agricultural intensification and provides useful information when deciding on priorities for mitigation.
JTP‐109192, a novel G protein‐coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolaemia in congenic spontaneously hyperlipidaemic mice
Authors: Tadaki Hironobu , Ogawa Naoto , Yamanaka Masao , Motohashi Yu , Sasase Tomohiko , Kawai Takashi , Toriniwa Yasufumi , Fukuda Sumiaki , Ogawa Nobuya , Harada Kazuhito , Ohta Takeshi , Yamada Takahisa
Published: October 2020

G protein‐coupled receptor 119 (GPR119) expression in pancreatic β‐cells and intestinal L‐cells is a potential therapeutic target for the treatment of type 2 diabetes. Previously, we have reported that the GPR119 agonist JTP‐109192 improves glucose metabolism with single and repeated administration. Conversely, overexpression of the Gpr119 gene reportedly regulates cholesterol transporter expression in animal models, and a natural GPR119 agonist, oleoylethanolamide (OEA), improves atherosclerosis. Therefore, improving dyslipidaemia is considered a possible feature of GPR119 agonists. In the present study, the lipid‐lowering effect of JTP‐109192 was examined in BALB/c background spontaneously hyperlipidaemic (SHL) mice with repeated administration, once daily for 12 weeks. On repeated administration, JTP‐109192 revealed a cholesterol‐lowering effect and improved atherosclerosis following histopathological examination. With further investigation, the cholesterol‐lowering effect and subsequent antiatherosclerotic effect of JTP‐109192 was attributed to changes in intestinal cholesterol metabolism gene expression. Based on these results, JTP‐109192 represents a new potential antihypercholesterolaemic agent for the treatment of dyslipidaemia.
Exploration of family intervention strategies and their receptivity among Chinese American families with a member having schizophrenia: a qualitative study
Authors: Kim Keon , Kung Winnie , Hong Inhwa
Published: October 2020

This study explores therapists’ specific intervention strategies and corresponding responses in the change process for Chinese American families with a family member having schizophrenia, based on individual family sessions notes in the context of family psychoeducation. Nine intake summaries and 103 family session notes (from nine patients and nineteen caregivers) were analysed through open, axial, and selective coding based on grounded theory. Interventions that promoted healthier family dynamics and effective communication, provided psychoeducation, practical help and emotional support, and improved coping skills were found to be effective and well received. These strategies can be integrated into a culturally sensitive family intervention protocol for this population and those of similar backgrounds. Clinicians can also employ them to enhance client receptivity in the treatment process.

Practitioner points

Many immigrant Chinese families with serious mental illness may become enmeshed, with caregivers exhibiting over‐involvement and criticism of sick family members

This increases stress for both parties and clinicians need to facilitate change to establish clear boundaries

Immigrant families often need help to meet their tangible needs in dealing with external systems in their daily lives

Understanding cultural characteristics among ethnic minorities and being flexible and responsive to their needs are both essential in family interventions.
Investigation of the relationship between the pelvic floor and sexual dysfunction in women with Sjögren’s syndrome
Authors: Cetin Sebahat Yaprak , Buyuk Alime , Ayan Ayse
Published: October 2020

Background and aim

Women with Sjögren's syndrome (SS) may have sexual dysfunctions due to vaginal dryness and may also have pelvic floor problems. The aim of this study was to examine the pelvic floor distress of women with SS with a self‐reported questionnaire, to compare this group with healthy individuals, and to examine the relationship between pelvic floor problems and sexual dysfunction.

Methods

The study included 94 women with SS, aged 47.26 ± 7.56 years, and 94 age‐matched healthy women, aged 48.15 ± 8.73 years. The Pelvic Floor Disease Inventory (PFDI‐20), Pelvic Floor Impact Questionnaire (PFIQ‐7), and Female Sexual Function Scale (FSFI) were used for assessment.

Results

The PFDI‐20, PFIQ‐7, and FSFI scores of the healthy control group were found to be statistically significantly better than those of the primary SS group (Z = −2.69 to −8.03, P = .00). A moderate‐high correlation was found between the total and sub‐parameters of PFDI‐20 and disease duration, the total and sub‐parameters of the PFIQ‐7 and the pain sub‐parameter and total score of the FSFI (r = −0.66 to 0.78, P = .00‐.04).

Conclusion

According to the study results, as the disease duration increases, the distress increases and this distress has a negative effect on the health‐related quality of life of these women. Pelvic floor distress was associated with poor sexual function and pain. From these results, it can be recommended that the methods of pharmacology, education, exercise, relaxation, lifestyle change, and so on for pelvic floor dysfunction and pain in women with SS should be applied together with a multidisciplinary approach.
Health System‐Based Unhealthy Alcohol Use Screening and Treatment Comparing Demographically Matched Participants With and Without HIV
Authors: Silverberg Michael J. , Levine‐Hall Tory , Hood Nicole , Anderson Alexandra N. , Alexeeff Stacey E. , Lam Jennifer O. , Slome Sally B. , Flamm Jason A. , Hare Charles Bradley , Ross Thekla , Justice Amy C. , Sterne Jonathan A. C. , Williams Andrew E. , Bryant Kendall J. , Weisner Constance M. , Horberg Michael A. , Sterling Stacy A. , Satre Derek D.
Published: October 2020

Background

Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care.

Methods

Cohort study of adult (≥18 years) PLWH and HIV‐uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider‐delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes.

Results

11,235 PLWH and 227,320 HIV‐uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV‐uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV‐uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year.

Conclusions

Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV‐uninfected participants.
Involvement of Cxcl12a/Cxcr4b Chemokine System in Mediating the Stimulatory Effect of Embryonic Ethanol Exposure on Neuronal Density in Zebrafish Hypothalamus
Authors: Collier Adam D. , Khalizova Nailya , Chang Guo‐Qing , Min Soe , Campbell Samantha , Gulati Gazal , Leibowitz Sarah F.
Published: October 2020

Background

Embryonic exposure to ethanol (EtOH) produces marked disturbances in neuronal development and alcohol‐related behaviors, with low–moderate EtOH doses stimulating neurogenesis without producing apoptosis and high doses having major cytotoxic effects while causing gross morphological abnormalities. With the pro‐inflammatory chemokine system, Cxcl12, and its main receptor Cxcr4, known to promote processes of neurogenesis, we examined here this neuroimmune system in the embryonic hypothalamus to test directly if it mediates the stimulatory effects low–moderate EtOH doses have on neuronal development.

Methods

We used the zebrafish (Danio rerio) model, which develops externally and allows one to investigate the developing brain in vivo with precise control of dose and timing of EtOH delivery in the absence of maternal influence. Zebrafish were exposed to low–moderate EtOH doses (0.1, 0.25, 0.5% v/v), specifically during a period of peak hypothalamic development from 22 to 24 hours postfertilization, and in some tests were pretreated from 2 to 22 hpf with the Cxcr4 receptor antagonist, AMD3100. Measurements in the hypothalamus at 26 hpf were taken of cxcl12a and cxcr4b transcription, signaling, and neuronal density using qRT‐PCR, RNAscope, and live imaging of transgenic zebrafish.

Results

Embryonic EtOH exposure, particularly at the 0.5% dose, significantly increased levels of cxcl12a and cxcr4b mRNA in whole embryos, number of cxcl12a and cxcr4b transcripts in developing hypothalamus, and internalization of Cxcr4b receptors in hypothalamic cells. Embryonic EtOH also caused an increase in the number of hypothalamic neurons and coexpression of cxcl12a and cxcr4b transcripts within these neurons. Each of these stimulatory effects of EtOH in the embryo was blocked by pretreatment with the Cxcr4 antagonist AMD3100.

Conclusions

These results provide clear evidence that EtOH’s stimulatory effects at low–moderate doses on the number of hypothalamic neurons early in development are mediated, in part, by increased transcription and intracellular activation of this chemokine system, likely due to autocrine signaling of Cxcl12a at its Cxcr4b receptor within the neurons.
Does correctional supervision of amphetamine users reduce the risk of re‐offending?
Authors: Weatherburn Don , Yeong Steve
Published: October 2020

Aim

To examine the specific deterrent effect of offender supervision on the risk of a further offence by persons convicted of amphetamine use and/or possession.

Design

Observational study of two groups matched on a wide range of factors using augmented inverse probability of treatment weighting.

Setting

New South Wales (NSW), Australia.

Participants

A total of 2099 persons convicted of amphetamine use and/or possession and placed on either a supervised good behaviour bond (1004) or a bond without supervision (1096).

Measurements

Conviction for another amphetamine use/possession offence, any drug offence, assault or theft within 48 months free time after the index court appearance.

Findings

Only two of the treatment estimates were consistent with a deterrent effect. Where the outcome was an assault offence, the estimated reduction in risk of re‐offending was 1%. Where the outcome was a theft offence, the estimated reduction in the risk of reoffending was 0.07%. Neither result was statistically significant. The coefficients measuring the effect of supervision on the remaining two outcomes (use/possess amphetamine and use/possess any drug) were both positive and not statistically significant.

Conclusion

Correctional supervision does not appear to have been effective in New South Wales, Australia, in reducing the risk of reoffending among people convicted of amphetamine use/possession.
Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis
Authors: Toyoshima Junko , Shibata Mai , Kaibara Atsunori , Kaneko Yuichiro , Izutsu Hiroyuki , Nishimura Tetsuya
Published: October 2020

Aims

To analyse the population pharmacokinetics (PK) of peficitinib in patients with rheumatoid arthritis (RA) and assess the potential PK covariates to identify the requirement for dose adjustment in RA patients.

Methods

The analysis incorporated 2464 observations from 98 healthy volunteers and 4919 observations from 989 RA patients. A population PK model for peficitinib in RA patients was constructed by a nonlinear mixed effect model using NONMEM with prior information from a healthy volunteer model.

Results

A 2‐compartment model with sequential zero‐ and first‐order absorption and lag time was constructed for RA patients. Covariate exploration in the RA patient model revealed that estimated glomerular filtration rate (eGFR) and lymphocyte count had a significant effect on apparent total systemic clearance (CL), which was 91.7 L/h (2.3% relative standard error). Compared with the mean population CL, the model predicted mean changes in CL of 12.3 and −10.7% in patients with observed minimum and maximum lymphocyte count of 500 and 4600 106/L, respectively, and mean changes in CL of −17.8 and 16.7% in patients with minimum and maximum eGFR of 36.4 and 188 mL/min/1.73m2, respectively. The simulated population mean area under plasma concentration–time curve for 24 hours after dosing showed a 1.35‐fold increase in patients with severe renal impairment (eGFR 22.5 mL/min/1.73m2) compared with patients with reference eGFR (91.5 mL/min/1.73m2).

Conclusion

The population PK model identified eGFR and lymphocyte count as covariates for CL. The magnitude of changes was not considered clinically relevant, indicating no requirement for dose adjustment.
Clinical outcomes of high‐intensity doses of atorvastatin in patients with acute coronary syndrome: A retrospective cohort study using real‐world data
Authors: Rahhal Alaa , Khir Fadi , Aljundi Amer Hussien , AlAhmad Yaser , Alzaeem Hakam , Habra Masa , Al‐Shekh Israa , Mahfouz Ahmed , Awaisu Ahmed , Al‐Yafei Sumaya , Arabi Abdul Rahman
Published: October 2020

Aims

To compare the effectiveness and safety of 2 high‐intensity atorvastatin doses (40 mg vs 80 mg) among acute coronary syndrome (ACS) patients.

Methods

This retrospective observational cohort study using real‐world data included patients admitted with ACS to the Heart Hospital in Qatar between 1 January 2017 and 31 December 2018. The primary endpoint was a composite of cardiovascular disease‐associated death, nonfatal ACS and nonfatal stroke. Cox proportional hazard regression analysis was used to determine the association between the 2 high‐intensity atorvastatin dosing regimens and the primary outcome at 1 month and 12 months postdischarge.

Results

Of the 626 patients included in the analyses, 475 (75.9%) received atorvastatin 40 mg, while 151 (24.1%) received atorvastatin 80 mg following ACS. Most of the patients were Asian (73%), male (97%) with a mean age of 50 years and presented with ST‐elevation myocardial infarction (60%). The incidence of the primary effectiveness outcome did not differ between the atorvastatin 40‐and 80‐mg groups at 1 month (0.8 vs 1.3%; adjusted hazard ratio = 0.59, 95% confidence interval 0.04–8.13, P = .690) and at 12 months (3.2 vs 4%; adjusted hazard ratio = 0.57, 95% confidence interval 0.18–1.80, P = .340). Similarly, the use of the 2 doses of atorvastatin resulted in comparable safety outcomes, including liver toxicity, myopathy and rhabdomyolysis with an event rate of <1% in both groups.

Conclusion

The use of atorvastatin 40 mg in comparison to atorvastatin 80 mg in patients with ACS resulted in similar cardiovascular effectiveness and safety outcomes.
Investigator brochures for phase I/II trials lack information on the robustness of preclinical safety studies
Authors: Sievers Sören , Wieschowski Susanne , Strech Daniel
Published: October 2020

Aim

Meaningful and ethical phase I/II trials can only be conducted with supportive prospective risk‐benefit assessment. This relies largely on preclinical animal studies addressing the safety and efficacy of treatments. These studies are reported in an Investigator's Brochure (IB) to inform ethics review boards and regulatory authorities. Our study investigated the extent, reporting quality and accessibility of preclinical safety studies (PCSSs) compiled in IBs.

Methods

We analysed a sample of 46 IBs for phase I/II trials approved at a leading German university medical centre from 2010 to 2016. We extracted all PCSSs presented in the 46 IBs and assessed them for reporting on methodological measures to reduce validity threats.

Results

The 46 IBs included 777 PCSSs. Blinded outcome assessment, randomization and sample size calculation were reported for fewer than 1% of studies. Only 5% of the PCSSs provided a reference to published data. Compliance with Good Laboratory Practice (GLP) guidance was reported for 52% of PCSSs, but the GLP document itself does not include any relevant methodological requirements for the reduction of validity threats.

Conclusion

Scarce reporting in IBs and the very limited publicly available data on PCSSs make it almost impossible for investigators to critically evaluate the robustness of preclinical evidence of drug safety. Combined with recent findings on the presentation of preclinical efficacy studies in IBs, we conclude that the current reporting patterns in IBs strongly limit the independent review of evidential support for early human trials. Regulatory authorities and IRBs should require better reporting in IBs.
Contractualist age rationing under outbreak circumstances
Authors: Nielsen Lasse
Published: October 2020

Age rationing is a central issue in the health care priority‐setting literature, but it has become ever more salient in the light of the Covid‐19 outbreak, where health authorities in several countries have given higher priority to younger over older patients. But how is age rationing different under outbreak circumstances than under normal circumstances, and what does this difference imply for ethical theories? This is the topic of this paper. The paper argues that outbreaks such as that of Covid‐19 involve special circumstances that change how age should influence our prioritization decisions, and that while this shift in circumstances poses a problem for consequentialist views such as utilitarianism and age‐weighted consequentialism, contractualism is better equipped to cope with it. The paper then offers a contractualist prudential account of age rationing under outbreak circumstances.
Social interaction and gender as factors affecting the trajectories of children's engagement and hyperactive behaviour in preschool
Authors: Sjöman Madeleine , Granlund Mats , Axelsson Anna Karin , Almqvist Lena , Danielsson Henrik
Published: October 2020

Background and aims

Social interactions in preschool and a child's gender are, in cross‐sectional studies, related to the child's overall levels of hyperactive behaviour and engagement in preschool activities. However, whether social interaction and gender can predict children's engagement and hyperactivity is not thoroughly investigated. This study aims to investigate the longitudinal influence of gender, child‐to‐child interaction, and teacher responsiveness on the association between trajectories of children's levels of core engagement and hyperactive behaviour. It was hypothesized that peer‐to‐child interaction and teacher responsiveness in preschool settings are related to positive change in engagement among children with hyperactive behaviour, especially for boys.

Sample and methods

Swedish preschool staff completed questionnaires assessing the variables of interest for children aged 1–5 (N = 203). Data were collected on three occasions over a two‐year period. Latent growth curve (LGC) models were used to explore whether teacher responsiveness, peer‐to‐child interaction, and gender predict trajectories of engagement and hyperactivity.

Results

The results revealed that high levels of hyperactivity were associated with lower levels of engagement on the first occasion. Positive peer‐to‐child interactions and responsive teachers were significant predictors of an increased level of engagement and decreased level of hyperactive behaviour, especially for boys.

Conclusions

The findings underscore the need to improve social interactions, especially peer‐to‐child interactions, to improve engagement in children with hyperactive behaviour, especially boys. Implications for practices and research are discussed.
Perceptual prioritization of self‐associated voices
Authors: Payne Bryony , Lavan Nadine , Knight Sarah , McGettigan Carolyn
Published: October 2020

Information associated with the self is prioritized relative to information associated with others and is therefore processed more quickly and accurately. Across three experiments, we examined whether a new externally‐generated voice could become associated with the self and thus be prioritized in perception. In the first experiment, participants learned associations between three unfamiliar voices and three identities (self, friend, stranger). Participants then made speeded judgements of whether voice‐identity pairs were correctly matched, or not. A clear self‐prioritization effect was found, with participants showing quicker and more accurate responses to the newly self‐associated voice relative to either the friend‐ or stranger‐ voice. In two further experiments, we tested whether this prioritization effect increased if the self‐voice was gender‐matched to the identity of the participant (Experiment 2) or if the self‐voice was chosen by the participant (Experiment 3). Gender‐matching did not significantly influence prioritization; the self‐voice was similarly prioritized when it matched the gender identity of the listener as when it did not. However, we observed that choosing the self‐voice did interact with prioritization (Experiment 3); the self‐voice became more prominent, via lesser prioritization of the other identities, when the self‐voice was chosen relative to when it was not. Our findings have implications for the design and selection of individuated synthetic voices used for assistive communication devices, suggesting that agency in choosing a new vocal identity may modulate the distinctiveness of that voice relative to others.
Targeted inhibition of Rev‐erb‐α/β limits ferroptosis to ameliorate folic acid‐induced acute kidney injury
Authors: Guo Lianxia , Zhang Tianpeng , Wang Fei , Chen Xun , Xu Haiman , Zhou Cui , Chen Min , Yu Fangjun , Wang Shuai , Yang Deguang , Wu Baojian
Published: October 2020

Background and Purpose

Acute kidney injury (AKI) is a common and critical illness, resulting in severe morbidity and a high mortality. There is a considerable interest in identifying novel molecular targets for management of AKI. We investigated the potential role of the circadian clock components Rev‐erb‐α/β in regulation of ferroptosis and AKI.

Experimental Approach

AKI model was established by treating mice with folic acid. Regulatory effects of Rev‐erb‐α/β on AKI and ferroptosis were determined using single‐gene knockout (Rev‐erb‐α−/− and Rev‐erb‐β−/−) mice, incomplete double‐knockout (icDKO, Rev‐erb‐α+/− Rev‐erb‐β−/−) mice and cells with erastin‐induced ferroptosis. Targeted antagonism of Rev‐erb‐α/β to alleviate AKI and ferroptosis was assessed using the small‐molecule antagonist SR8278. Transcriptional gene regulation was investigated using luciferase reporter, mobility shift and chromatin immunoprecipitation assays.

Key Results

Loss of Rev‐erb‐α or Rev‐erb‐β reduced the sensitivity of mice to folic acid‐induced AKI and eliminated the circadian time dependency in disease severity. This coincided with less extensive ferroptosis, a main cause of folic acid‐induced AKI. Moreover, icDKO mice were more resistant to folic acid‐induced AKI and ferroptosis as compared with single‐gene knockout mice. Supporting this, targeting Rev‐erb‐α/β by SR8278 attenuated ferroptosis to ameliorate folic acid‐induced AKI in mice. Rev‐erb‐α/β promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis‐inhibitory genes) via direct binding to a RORE cis‐element.

Conclusion and Implications

Targeted inhibition of Rev‐erb‐α/β limits ferroptosis to ameliorate folic acid‐induced AKI in mice. The findings may have implications for improved understanding of circadian clock‐controlled ferroptosis and for formulating new strategies to treat AKI.
ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus‐dependent E‐cadherin downregulation
Authors: Otake Shigeo , Itoh Yuka , Omata Chiho , Saitoh Masao , Miyazawa Keiji
Published: October 2020

E‐cadherin, an epithelial cell–specific cell adhesion molecule, has both promoting and suppressing effects on tumor invasion and metastasis. It is often downregulated during cancer progression through gene deletion/mutation, transcriptional repression, or epigenetic silencing. We describe a novel regulatory switch to induce stimulus‐dependent downregulation of mRNA encoding E‐cadherin (CDH1 mRNA) in KRAS‐mutated cancer cells. The regulatory switch consists of ZEB1 and oncogenic K‐Ras, does not target the promoter region of CDH1, and requires an external cue to temporally downregulate E‐cadherin expression. Its repressive effect is maintained as long as the external stimulus continues and is attenuated with cessation of the stimulus. Contextual external cues that turn this regulatory switch on include activation of protein kinase C or fibroblast growth factor signaling. The mode of action is distinct from that of EPCAM repression by ZEB1, which does not require an external cue. Thus, KRAS‐mutated cancer cells acquire a novel mode of regulating E‐cadherin expression depending on ZEB1, which could contribute to phenotypic plasticity of cancer cells during malignant progression.
Oncogenic KRAS–expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice
Authors: Kasuga Akiyoshi , Semba Takashi , Sato Ryo , Nobusue Hiroyuki , Sugihara Eiji , Takaishi Hiromasa , Kanai Takanori , Saya Hideyuki , Arima Yoshimi
Published: October 2020

Biliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)–positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC–initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three‐dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial‐mesenchymal transition (EMT)–related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC–initiating cells.
Bridging gaps in demographic analysis with phylogenetic imputation
Authors: James Tamora D. , Salguero‐Gómez Roberto , Jones Owen R. , Childs Dylan Z. , Beckerman Andrew P.
Published: October 2020

Phylogenetically informed imputation methods have rarely been applied to estimate missing values in demographic data but may be a powerful tool for reconstructing vital rates of survival, maturation, and fecundity for species of conservation concern. Imputed vital rates could be used to parameterize demographic models to explore how populations respond when vital rates are perturbed. We used standardized vital rate estimates for 50 bird species to assess the use of phylogenetic imputation to fill gaps in demographic data. We calculated imputation accuracy for vital rates of focal species excluded from the data set either singly or in combination and with and without phylogeny, body mass, and life‐history trait data. We used imputed vital rates to calculate demographic metrics, including generation time, to validate the use of imputation in demographic analyses. Covariance among vital rates and other trait data provided a strong basis to guide imputation of missing vital rates in birds, even in the absence of phylogenetic information. Mean NRMSE for null and phylogenetic models differed by <0.01 except when no vital rates were available or for vital rates with high phylogenetic signal (Pagel'sλ >0.8). In these cases, including body mass and life‐history trait data compensated for lack of phylogenetic information: mean normalized root mean square error (NRMSE) for null and phylogenetic models differed by <0.01 for adult survival and <0.04 for maturation rate. Estimates of demographic metrics were sensitive to the accuracy of imputed vital rates. For example, mean error in generation time doubled in response to inaccurate estimates of maturation time. Accurate demographic data and metrics, such as generation time, are needed to inform conservation planning processes, for example through International Union for Conservation of Nature Red List assessments and population viability analysis. Imputed vital rates could be useful in this context but, as for any estimated model parameters, awareness of the sensitivities of demographic model outputs to the imputed vital rates is essential.
Increased arterial stiffness and reduced left ventricular long‐axis function in patients recovered from peripartum cardiomyopathy
Authors: Johansson Magnus C. , Barasa Anders , Basic Carmen , Nyberg Gunnar , Schaufelberger Maria
Published: October 2020

Background

Peripartum cardiomyopathy (PPCM) is idiopathic pregnancy‐associated heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We aimed to assess arterial stiffness and left ventricular (LV) function in women recovered from PPCM compared with controls.

Methods

Twenty‐two PPCM patients were compared with 15 age‐matched controls with previous uncomplicated pregnancies. Eleven of the patients were at inclusion in the study recovered and off medication since at least 6 months and still free from cardiovascular symptoms with normal LVEF and normal NT‐proBNP. All underwent echocardiography, including LV strain, left atrial (LA) reservoir strain and tissue Doppler early diastolic velocity (e´) and non‐invasive assessment for arterial stiffness and central aortic systolic blood pressure (AoBP) at rest and immediately postexercise.

Results

The patients off medication showed alterations compared with controls. AoBP was higher (120 ± 9 mm Hg vs. 104 ± 13 mm Hg; p = .001), a difference which persisted postexercise. The arterial elastance was higher (1.9 ± 0.4 mm Hg/ml vs. 1.3 ± 0.2 mm Hg/ml; p < .001), while there were lower e´ septal (8.9 ± 1.7 cm/s vs. 11.0 ± 1.1 cm/s; p = 0. 002), LV global strain (18.7 ± 3.9% vs. 23.1 ± 1.6%; p = .004) and LA reservoir strain (24.8 ± 9.1% vs. 37.7 ± 6.3%; p = .002).

Conclusions

Compared with healthy controls, PPCM patients considered recovered and off medication had increased arterial stiffness, decreased LV longitudinal function and reduced LA function.
Spitz nevi in African Americans: A retrospective chart review of 11 patients
Authors: Farid Yostina I. , Honda Kord S.
Published: October 2020

Background

Spitz nevi are benign melanocytic neoplasms that typically present as rapidly growing solitary lesions on the head, neck, or lower extremities. Very rare reports have been described in African Americans.

Methods

A single‐institution 29‐year retrospective review of African American patients diagnosed with Spitz nevi was thoroughly analyzed in order to characterize these rare clinical and histopathologic presentations.

Results

Eleven African Americans with spitzoid lesions were identified. Seven (64%) cases were in pediatric patients and nine (82%) were in females. Most lesions were hyperpigmented (73%) and elevated (82%). Six (55%) were compound Spitz nevi, three (27%) were dermal Spitz nevi, and two (18%) were junctional Spitz nevi. Two lesions had more than one atypical feature. Histopathologically, common features were symmetry, sharp circumscription, pagetoid spread (55%) with most being centrally, predominance of epithelioid cells (64%), Kamino bodies (45%), slight pigmentation (46%), maturation of dermal component with depth, and lack of subcutaneous fat involvement or ulceration. Excision was performed on all patients and there were no recurrences although follow‐up was limited.

Conclusion

Awareness of the possibility and various presentations of Spitz nevi in African Americans will help prevent misdiagnosis.
Malignant onychopapilloma
Authors: Haneke Eckart , Iorizzo Matilde , Gabutti Max , Beltraminelli Helmut
Published: October 2020

Onychopapilloma is a fairly common lesion that is clinically typical enough to make the diagnosis. It is unique in that it stretches from the distal matrix all along the nailbed to the hyponychium. A case is described that developed pain eventually resulting in total excision. Histopathology revealed a malignant onychopapilloma. The differential diagnosis of this lesion is discussed.
Mechanisms underlying host persistence following amphibian disease emergence determine appropriate management strategies
Authors: Brannelly Laura A. , McCallum Hamish I. , Grogan Laura F. , Briggs Cheryl J. , Ribas Maria P. , Hollanders Matthijs , Sasso Thais , Familiar López Mariel , Newell David A. , Kilpatrick Auston M.
Published: October 2020

Emerging infectious diseases have caused many species declines, changes in communities and even extinctions. There are also many species that persist following devastating declines due to disease. The broad mechanisms that enable host persistence following declines include evolution of resistance or tolerance, changes in immunity and behaviour, compensatory recruitment, pathogen attenuation, environmental refugia, density‐dependent transmission and changes in community composition. Here we examine the case of chytridiomycosis, the most important wildlife disease of the past century. We review the full breadth of mechanisms allowing host persistence, and synthesise research on host, pathogen, environmental and community factors driving persistence following chytridiomycosis‐related declines and overview the current evidence and the information required to support each mechanism. We found that for most species the mechanisms facilitating persistence have not been identified. We illustrate how the mechanisms that drive long‐term host population dynamics determine the most effective conservation management strategies. Therefore, understanding mechanisms of host persistence is important because many species continue to be threatened by disease, some of which will require intervention. The conceptual framework we describe is broadly applicable to other novel disease systems.