bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of landscape composition and configuration on crop yield resilience
Authors: Redhead John W. , Oliver Tom H. , Woodcock Ben A. , Pywell Richard F.
Published: July 2020

Sustainable agriculture aims to produce sufficient food while minimizing environmental damage. To achieve this, we need to understand the role of agricultural landscapes in providing diverse ecosystem services and how these affect crop production and resilience, that is, maintaining yields despite environmental perturbation.

We used 10 years of English wheat yield data to derive three metrics of resilience (relative yield across the time series, yield stability around a moving average and resistance to an extreme weather event) at 10 km × 10 km resolution. We used remotely sensed maps to calculate measures of landscape structure, including composition (proportions of different land cover types) and configuration (metrics of connectivity and proximity), known to affect ecosystem service delivery (e.g. control of pests by beneficial invertebrates). We then used an information‐theoretic approach to identify the best‐fitting combination of landscape structure predictors for each resilience metric, using a potential yield model to account for the effects of climate and soils.

Relative yield showed a strongly positive relationship with the area of arable land. For yield stability, this relationship was evident but alongside other landscape structure variables in the best‐fitting model. No relationship with arable land was evident for resistance.

Yield stability showed a strongly positive effect of proximity to semi‐natural habitats. For resistance, the best‐fitting model included positive relationships with the cover of semi‐natural habitats and proximity to semi‐natural grasslands.

Synthesis and applications. Landscapes with the highest relative wheat yields did not show the highest yield stability or resistance to extreme events. As resilience metrics were derived from shorter portions of the time series, the importance of semi‐natural habitats compared to arable land increased. This is probably driven by the complex interplay between landscape structure, agricultural management and ecosystem services. These results demonstrate that measuring relative yield over time may be insufficient to capture the full effect that non‐arable components of the landscape, and the ecosystem services they deliver, have on other aspects of resilience, and that there are clear trade‐offs in managing agricultural landscapes to maximize different aspects of crop yield resilience.
Farm machinery use and maize yields in China: an analysis accounting for selection bias and heterogeneity
Authors: Zhou Xiaoshi , Ma Wanglin , Li Gucheng , Qiu Huanguang
Published: July 2020

Crop production in developing and emerging countries is increasingly dependent on the usage of farm machinery. However, it remains unclear whether low‐productive and high‐productive farmers benefit equally from farm machinery use. To address the research gap, this study examines the potential heterogeneous effects of farm machinery use on maize yields, using an unconditional quantile regression model and survey data from China. We employ a control function approach to address the selection bias issue associated with farm machinery use. The empirical results show that the use of farm machinery significant increases maize yields for all the selected quantiles (except for the 80th quantile); the low‐productive farmers tend to benefit more from farm machinery use relative to their high‐productive counterparts; and farm machinery use reduces the inequality and variability of maize yields.
Conclusion: Four Recommendations to Improve Digital Electoral Oversight in the UK
Authors: Margetts Helen , Dommett Katharine
Published: July 2020

To conclude this special section, this article looks at the possible avenues for regulatory reform in the field of digital campaigning. Diagnosing the need for a multi‐layered approach, we argue that action is needed from government, regulators, companies, and civil society. We take each actor in turn and consider the kind of change needed, the prospects for reform, and outline four recommendations for change.
Fresh‐cut potato quality and sensory: Effect of cultivar, age, processing, and cooking during storage
Authors: Dite Hunjek Draženka , Pranjić Tanja , Repajić Maja , Levaj Branka
Published: July 2020

This work examined the influence of cultivar, tubers’ age, antibrowning agent, package atmosphere, and storage time on fresh‐cut potatoes’ (FCPs) physical, chemical, and sensory properties. Potato slices of cv. Birgit and Lady Claire tubers sampled during the first, fifth, and ninth months of storage were dipped in solutions of (1) sodium chloride (1%) and (2) sodium ascorbate (2%), and stored for 8 days in (1) vacuum and (2) active modified atmosphere (MAP) (10.0% CO2, 3.0% O2, and 87.0% N2) at 10 °C. During storage, O2 and CO2 content (%) within packages was measured and samples were analyzed for weight loss, total solids (TS) and soluble solids (SS), pH, color, texture, and sensory properties of raw, boiled, fried, and baked FCP. Results showed that 9 months' aging had a significant impact on almost all investigated FCP properties, but differences among first, fifth, and ninth months were numerically feeble for some parameters in raw samples: TS changed from 22.14% to 20.98%, SS 5.53% to 6.93%, pH 6.02 to 5.98, L* 70.10 to 68.87, C* 35.75 to 36.70, H° 89.29 to 88.15, and firmness 7.25 to 8.13N. Furthermore, 9 months of aging had no significant influence on the characteristic odor of raw, boiled, fried, and baked FCP and characteristic taste of fried and baked FCP, whereas boiled FCP characteristic taste remained unchanged for 5 months of aging. Fried FCP was better sensory evaluated than baked ones, cv. Birgit was more suitable for the FCP production compared to cv. Lady Claire as well as vacuum packaging and sodium ascorbate better preserved samples quality and sensory than sodium chloride and MAP.

Practical Application

This study could be helpful to fresh‐cut potato (FCP) producers because results indicate that for FCP processing, along with the selection of cultivar, antibrowning agent, and packaging type, tubers’ age also requires attention. A further contribution of this research is related to the adequate way of FCP cooking, where frying shows the best results according to the quality and sensory assessment.
Vector transmission of konjac mosaic virus to calla lily (Zantedeschia spp.) by aphids
Authors: Liao Min‐Ting , Mou De‐Fen , Chang Ya‐Chun , Tsai Chi‐Wei
Published: July 2020

Various viral diseases and bacterial soft rot are the major limiting factors for the cultivation of calla lilies (Zantedeschia spp.). Konjac mosaic virus (KoMV) is one of the major causal agents of viral diseases in calla lily fields in Taiwan. The objectives of this study are to identify potential insect vectors of KoMV and to assess the biotic and abiotic factors affecting aphid transmission of KoMV to calla lily. In this study, we identified Myzus persicae and Aphis gossypii as potential vectors of KoMV. Early‐instar nymphs, late‐instar nymphs, apterous adults and alate adults of both aphid species were able to transmit KoMV, and no significant differences in the transmission rates were detected. The difference in KoMV transmission rates was not detected when the transmission assays were performed at 18, 23 and 28°C. Transmission biology is a crucial component of plant disease epidemiology caused by viruses. Vector propensity and vector activity need to be further investigated in the field. The knowledge will be valuable for developing disease control strategies for KoMV in calla lily fields.
Executive Compensation and Company Valuation
Authors: Schueler Andreas
Published: July 2020

In the literature, the integration of the cash and risk effects of executive compensation into company valuation is discussed only marginally. This paper addresses the question of how these effects can be integrated into corporate valuation. Several methods for solving the problem are discussed and a method free of circular references, similar to the adjusted present value approach to company valuation, is identified. Contrary to a common assumption in the literature, there is no uniform and constant cost of capital for a company that uses employee stock options. Cost of capital needs to be adjusted to the cash and risk impact of equity‐based executive compensation. Making recourse to the treasury stock method, which is used to calculate diluted earnings per share, is not recommended here even though a corrected version of this method is used. I discuss different forms of equity‐based executive compensation, including the resulting allocation of risk and net present value between owners and managers.
Targeting RAS‐converting enzyme 1 overcomes senescence and improves progeria‐like phenotypes of ZMPSTE24 deficiency
Authors: Yao Haidong , Chen Xue , Kashif Muhammad , Wang Ting , Ibrahim Mohamed X. , Tüksammel Elin , Revêchon Gwladys , Eriksson Maria , Wiel Clotilde , Bergo Martin O.
Published: July 2020

Several progeroid disorders are caused by deficiency in the endoprotease ZMPSTE24 which leads to accumulation of prelamin A at the nuclear envelope. ZMPSTE24 cleaves prelamin A twice: at the third carboxyl‐terminal amino acid following farnesylation of a –CSIM motif; and 15 residues upstream to produce mature lamin A. The carboxyl‐terminal cleavage can also be performed by RAS‐converting enzyme 1 (RCE1) but little is known about the importance of this cleavage for the ability of prelamin A to cause disease. Here, we found that knockout of RCE1 delayed senescence and increased proliferation of ZMPSTE24‐deficient fibroblasts from a patient with non‐classical Hutchinson‐Gilford progeria syndrome (HGPS), but did not influence proliferation of classical LMNA‐mutant HGPS cells. Knockout of Rce1 in Zmpste24‐deficient mice at postnatal week 4–5 increased body weight and doubled the median survival time. The absence of Rce1 in Zmpste24‐deficient fibroblasts did not influence nuclear shape but reduced an interaction between prelamin A and AKT which activated AKT‐mTOR signaling and was required for the increased proliferation. Prelamin A levels increased in Rce1‐deficient cells due to a slower turnover rate but its localization at the nuclear rim was unaffected. These results strengthen the idea that the presence of misshapen nuclei does not prevent phenotype improvement and suggest that targeting RCE1 might be useful for treating the rare progeroid disorders associated with ZMPSTE24 deficiency.
Socio‐demographic differences in alcohol‐related work impairment
Authors: Moan Inger Synnøve , Halkjelsvik Torleif
Published: July 2020

Background and Aims

The costs of alcohol‐related presenteeism (being at work in an impaired state due to alcohol use) have been estimated as substantially larger than the costs of alcohol‐related absenteeism. Past studies indicate that employees with lower socio‐economic status experience more alcohol‐attributable problems than employees in higher socio‐economic strata. We aimed to estimate the prevalence of alcohol‐related presenteeism among Norwegian adults and its association with sex, age, income and education.

Design and Setting

Annual national cross‐sectional telephone surveys on alcohol, tobacco and drug use (2016–19) among Norwegian adults.

Participants

A total of 5430 full‐ and part‐time employees aged 16–79 years; 53% were men.

Measurements

The main outcome was self‐reported 12‐month occurrence of work impairment due to alcohol use the previous day. Main predictors were income and education obtained from national registries, age and gender. A secondary outcome variable was self‐reported alcohol‐related absenteeism.

Findings

The 12‐month prevalence of alcohol‐related work impairment was 8.7%, 95% confidence interval (CI) = 7.9, 9.4. Adjusted risk ratios (RR) indicated a higher risk for men compared with women (RR = 1.26, 95% CI = 1.06, 1.50) and higher risk for young employees (e.g. less than 26 years compared with 55+, RR = 7.64, 95% CI = 4.88, 11.95). The risk increased as a function of higher education (in order of increasing education, RR = 1.12, 95% CI = 0.87, 1.45; RR = 1.64, 95% CI = 1.26, 2.12; RR = 2.19, 95% CI = 1.63, 2.95). The risk was estimated as lower in the middle‐income categories compared with the lowest (RR = 0.76, 95% CI = 0.58, 1.00, RR = 0.89, 95% CI = 0.66, 1.20, RR = 0.94, 95% CI = 0.68, 1.29) and higher for employees with the highest income (RR = 1.04, 95% CI = 0.73, 1.48; RR = 1.47, 95% CI = 1.09, 2.00).

Conclusions

In Norway, the risk of alcohol‐related work impairment for employees in the highest education category is approximately twice that of employees with secondary education or less. Except for employees in the lowest income category, who had a higher risk than those in the middle‐income categories, higher income is associated with increased risk of work impairment. Being younger and male are also associated with increased risk of alcohol‐related work impairment.
Novel use of cangrelor in pediatrics: A pilot cohort study demonstrating use in ventricular assist devices
Authors: Fahnhorst Sarah E. , Beasley Gary , Goldberg Jason F. , Martinez Hugo R. , Ryan Kaitlin A. , Towbin Jeffrey A. , Boston Umar , Absi Mohammed
Published: July 2020

Thromboembolic events and bleeding are major sources of morbidity among pediatric patients supported on a ventricular assist device (VAD). Pharmacokinetics and pharmacodynamics of enteral antiplatelet agents are affected and variable due to erratic enteral absorption in end‐stage heart failure and VAD circulation. Additionally, 20%‐40% of the population are poor metabolizers of clopidogrel, a prodrug, making cangrelor an alternative when antiplatelet therapy is crucial. Cangrelor has been used effectively and safely for short durations in adults during percutaneous coronary interventions, but the use of cangrelor is still under investigation in pediatrics. This case series utilized cangrelor, a novel short‐acting, reversible, intravenous P2Y12 platelet inhibitor in managing pediatric patients supported with a VAD. We performed a retrospective, single‐center review of patients admitted to a tertiary medical center with end‐stage heart failure requiring mechanical circulatory support and concomitant cangrelor administration between January 2019 and March 2020. Platelet function testing, cangrelor dose, bleeding complications, thromboembolic events, and frequency of circuit interventions during the use of cangrelor were recorded. Optimal platelet reactivity, defined as P2Y12 < 180 platelet reaction units (PRU), was measured with serial point‐of‐care testing (VerifyNow). Seven patients, median age of 4.9 years, met the above criteria. Three patients had a diagnosis of complex congenital heart disease. Four patients had dilated or restrictive cardiomyopathy. All patients were on continuous flow VADs. The median VAD duration was 84.5 days (IQR 61.5‐103). The median duration on cangrelor was 43 days (IQR 8‐70). The median cangrelor dose to reach the therapeutic threshold was 0.75 μg/kg/min with the mean P2Y12, while on cangrelor of 164.75 PRU. Bleeding complications included mild gastrointestinal bleeding and hematuria. There was one patient with pump thrombosis requiring intervention. There were no cerebrovascular events while on cangrelor. We report the first successful long‐term use of cangrelor in pediatric patients. The reversibility and short half‐life of cangrelor make it a feasible antiplatelet agent in selected patients. This data supports the use of cangrelor in children as a viable antiplatelet option; with minimal bleeding complications and no cerebrovascular events demonstrated in this cohort.
Comparison of myopic progression in Finnish and Singaporean children
Authors: Pärssinen Olavi , Soh Zhi Da , Tan Chuen‐Seng , Lanca Carla , Kauppinen Markku , Saw Seang‐Mei
Published: July 2020

Purpose

To compare 3‐year myopic progression between Finnish and Singaporean children.

Methods

Myopic progression was compared between 9‐year‐old (mean age 9.7 ± 0.4 years, n = 92) and 11‐year‐old (mean age 11.7 ± 0.4 years, n = 144) Finnish (Finnish RCT) children and Singaporean children matched by age and refraction (SCORMMatched, n = 403) and 7‐ to 8‐year‐old Singaporean children matched only by refraction (SCORM Young, n = 186). Spherical equivalent (SE) was between −0.50 and −3.00 D. Refraction with cycloplegia was controlled annually for 3 years. Information on parental myopia, mother’s education, time spent on near‐work and outdoor time was gathered by parental questionnaire.

Results

Three‐year myopic progression was −2.08 ± 0.96 D and −1.30 ± 0.69 D in the Finnish RCT and Singaporean SCORM

Matched 9‐year‐olds, respectively, and −1.34 ± 0.78 D, and −0.52 ± 0.44 D in the 11‐year‐olds, respectively (p < 0.001 between all groups). Myopic progression was fastest (−2.69 ± 0.89 D) in the SCORM 7‐year‐olds and similar between the SCORM Matched 9‐year‐olds and Finnish RCT 11‐year‐olds (p = 0.55). The Finnish RCT and SCORM Matched children showed significant differences in both daily near‐work time (1.8 ± 1.0 versus 3.4 ± 1.9 hours per day, p < 0.001) and outdoor time (2.6 ± 0.9 versus 0.5 ± 0.4 hours per day, p < 0.001). These differences did not, however, explain the differences in myopic progression between the groups. More time spent outdoors was associated with less myopic progression in the Finnish RCT (r = 0.17, p = 0.009) group only. In the whole materials, greater myopic progression was associated with younger age at baseline (p < 0.001), younger age was associated with mother’s higher education (p < 0.001), and mothers higher education was associated with myopia in both parents (p < 0.001).

Conclusion

Age at baseline was the most significant factor associated with myopic progression. However, at the same age and with the same initial refraction, the Finnish and Singaporean children showed different myopic progression. This result remains unexplained. Thus, age of myopia onset should be considered when comparing myopic progression between different samples and conducting treatment trials. Parental myopia may be a weak indicator of heredity of myopia.
Paediatric infections in the first 3 years of life after maternal anti‐TNF treatment during pregnancy
Authors: Bröms Gabriella , Kieler Helle , Ekbom Anders , Gissler Mika , Hellgren Karin , Leinonen Maarit K. , Pedersen Lars , Schmitt‐Egenolf Marcus , Sørensen Henrik Toft , Granath Fredrik
Published: July 2020

Background

Most anti‐tumour necrosis factor (anti‐TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.

Aims

To assess the risk of paediatric infections after maternal anti‐TNF treatment.

Methods

Population‐based cohort study in Denmark, Finland and Sweden 2006‐2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti‐TNF, and 9346 children to women with non‐biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.

Results

Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23‐1.67) for anti‐TNF and 1.14 (1.07‐1.21) for non‐biologic systemic treatment, and 1.29 (1.11‐1.50) and 1.09 (1.02‐1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti‐TNF, 1.19 (1.11‐1.29), and for non‐biologic systemic treatment, 1.10 (1.07‐1.13). There was no difference among anti‐TNF agents, treatment in the third trimester, or between mono/combination therapy with non‐biologic systemic treatment.

Conclusions

Both anti‐TNF and non‐biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare‐seeking behaviour. This may in turn shift the risk‐benefit equation towards continuation of treatment even in the third trimester.
Changes in plant functional composition of wetland vegetation along an aridity gradient on the Highveld plateau of South Africa
Authors: Mofutsanyana Seadi S. , Collins Nacelle B. , Adelabu Samuel A. , Chatanga Peter , Sieben Erwin J. J.
Published: July 2020

Question

Plant communities will change along environmental gradients, even in “azonal” vegetation such as wetlands. It is hypothesized that functional community composition of wetland vegetation changes along a natural gradient from dry low‐lying areas to wet high‐lying areas. We wanted to know how the functional groups that make up wetland plant communities change along such aridity and altitudinal gradients.

Location

Highveld area of Central South Africa, covering four provinces of the country: Northern Cape, Free State, North West and Mpumalanga.

Methods

The community composition of 201 vegetation plots was obtained from a compilation of South African wetland vegetation types of the study area. Functional traits were collected for the dominant plant species and community‐weighted means of plant functional traits were calculated for wetland vegetation plots. Redundancy analysis was performed to plot these against environmental and climatic gradients.

Results

The ordination results showed that the community‐weighted plant functional traits were correlated with environmental and climatic variables. For example, specific correlations reveal that root/shoot biomass ratio, leaf nitrogen and specific leaf area are associated with high temperature and evaporation, conditions that prevail in the driest end of the gradient. On the opposite end, wetland vegetation in mesic areas has adaptations for fast growth and high productivity, as it is composed of tall plants with wide stems and deep roots. A hierarchical cluster analysis (HCA) resulted in nine plant functional groups, with different representation along the aridity gradient in the Highveld Plateau of South Africa.

Conclusions

Wetlands in dry areas have plant functional groups different from those in mesic areas. Changes in community composition show how wetlands are responding to climatic variability and environmental change. Thus, the study of changes in plant functional groups can be useful for detecting the impacts of climate change on wetland vegetation.
Loss of capillary pericytes and the blood–brain barrier in white matter in poststroke and vascular dementias and Alzheimer’s disease
Authors: Ding Ren , Hase Yoshiki , Ameen‐Ali Kamar E. , Ndung'u Michael , Stevenson William , Barsby Joseph , Gourlay Ryan , Akinyemi Tolulope , Akinyemi Rufus , Uemura Maiko T. , Polvikoski Tuomo , Mukaetova‐Ladinska Elizabeta , Ihara Masafumi , Kalaria Raj N.
Published: July 2020

White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood–brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected to the frontal lobe WM capillaries. Pericytes with a nucleus were identified by collagen 4 (COL4) and platelet‐derived growth factor receptor‐β (PDGFR‐β) antibodies with further verification using PDGFR‐β‐specific ELISA. We evaluated a total of 124 post‐mortem brains from subjects with post‐stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), AD‐VaD (Mixed) and post‐stroke non‐demented (PSND) stroke survivors as well as normal aging controls. COL4 and PDGFR‐β reactive pericytes adopted the characteristic “crescent” or nodule‐like shapes around capillary walls. We estimated densities of pericyte somata to be 225 ±38 and 200 ±13 (SEM) per COL4 mm2 area or 2.0 ± 0.1 and 1.7 ± 0.1 per mm capillary length in young and older aging controls. Remarkably, WM pericytes were reduced by ~35%–45% in the frontal lobe of PSD, VaD, Mixed and AD subjects compared to PSND and controls subjects (P < 0.001). We also found pericyte numbers were correlated with PDGFR‐β reactivity in the WM. Our results first demonstrate a reliable method to quantify COL4‐positive pericytes and then, indicate that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD. Our findings suggest that downregulation of pericytes is associated with the disruption of the BBB in the deep WM in several aging‐related dementias.
What is philosophy as a way of life? Why philosophy as a way of life?
Authors: Grimm Stephen R. , Cohoe Caleb
Published: July 2020

Despite a recent surge of interest in philosophy as a way of life, it is not clear what it might mean for philosophy to guide one's life, or how a “philosophical” way of life might differ from a life guided by religion, tradition, or some other source. We argue against John Cooper that spiritual exercises figure crucially in the idea of philosophy as a way of life—not just in the ancient world but also today, at least if the idea is to be viable. In order to make the case we attempt to clarify the nature of spiritual exercises, and to explore a number of fundamental questions, such as “What role does reason have in helping us to live well?” Here we distinguish between the discerning and motivational powers of reason, and argue that both elements have limitations as guides to living well.
Ecological impacts of human‐induced animal behaviour change
Authors: Wilson Margaret W. , Ridlon April D. , Gaynor Kaitlyn M. , Gaines Steven D. , Stier Adrian C. , Halpern Benjamin S.
Published: July 2020

A growing body of literature has documented myriad effects of human activities on animal behaviour, yet the ultimate ecological consequences of these behavioural shifts remain largely uninvestigated. While it is understood that, in the absence of humans, variation in animal behaviour can have cascading effects on species interactions, community structure and ecosystem function, we know little about whether the type or magnitude of human‐induced behavioural shifts translate into detectable ecological change. Here we synthesise empirical literature and theory to create a novel framework for examining the range of behaviourally mediated pathways through which human activities may affect different ecosystem functions. We highlight the few empirical studies that show the potential realisation of some of these pathways, but also identify numerous factors that can dampen or prevent ultimate ecosystem consequences. Without a deeper understanding of these pathways, we risk wasting valuable resources on mitigating behavioural effects with little ecological relevance, or conversely mismanaging situations in which behavioural effects do drive ecosystem change. The framework presented here can be used to anticipate the nature and likelihood of ecological outcomes and prioritise management among widespread human‐induced behavioural shifts, while also suggesting key priorities for future research linking humans, animal behaviour and ecology.
Precision medicine and therapies of the future
Authors: Sisodiya Sanjay M.
Published: July 2020

Precision medicine in the epilepsies has gathered much attention, especially with gene discovery pushing forward new understanding of disease biology. Several targeted treatments are emerging, some with considerable sophistication and individual‐level tailoring. There have been rare achievements in improving short‐term outcomes in a few very select patients with epilepsy. The prospects for further targeted, repurposed, or novel treatments seem promising. Along with much‐needed success, difficulties are also arising. Precision treatments do not always work, and sometimes are inaccessible or do not yet exist. Failures of precision medicine may not find their way to broader scrutiny. Precision medicine is not a new concept: It has been boosted by genetics and is often focused on genetically determined epilepsies, typically considered to be driven in an individual by a single genetic variant. Often the mechanisms generating the full clinical phenotype from such a perceived single cause are incompletely understood. The impact of additional genetic variation and other factors that might influence the clinical presentation represent complexities that are not usually considered. Precision success and precision failure are usually equally incompletely explained. There is a need for more comprehensive evaluation and a more rigorous framework, bringing together information that is both necessary and sufficient to explain clinical presentation and clinical responses to precision treatment in a precision approach that considers the full picture not only of the effects of a single variant, but also of its genomic and other measurable environment, within the context of the whole person. As we may be on the brink of a treatment revolution, progress must be considered and reasoned: One possible framework is proposed for the evaluation of precision treatments.
Women with drug‐resistant epilepsy: Surgery or pregnancy first?
Authors: Kandraju Sai Satish , Jose Manna , Salini Reshma A. , Pavithran Veena , Samuel Peedicail Joseph , Menon Ramsekhar N. , Radhakrishnan Ashalatha , Cherian Ajith , Abraham Mathew , Vilanilam George C. , Thomas Sanjeev V.
Published: July 2020

Objective

We compared women with drug‐resistant focal epilepsy who had undergone surgery (WWE‐S) with those who were managed medically (WWE‐M) for maternal and fetal outcomes of their pregnancies.

Methods

We classified all WWE‐S who were enrolled in a prospective registry of epilepsy and pregnancy (1998‐2015) as those who underwent the surgery before pregnancy (WWE‐SF) or after pregnancy (WWE‐PF). The comparator group (WWE‐M) was twice that number of age‐matched women with focal epilepsy in this registry. Their clinical profile, anti‐epileptic drug (AED) use, and pregnancy outcomes were extracted from the records of the registry.

Results

The number of completed pregnancies with known outcome was 74 for WWE‐S (67 WWE‐SF and 7 WWE‐PF) and 134 for WWE‐M. Seizures increased during pregnancy for fewer WWE‐SF than for WWE‐M (14.9% vs 39.6%, P = .001). Compared to WWE‐M, fewer WWE‐SF had dose escalation during pregnancy (28.4% vs 14.9%, P = .025). Preterm deliveries were more frequent in WWE‐SF than WWE‐M (24.6% vs 12.2%, P = .029). The differences between the WWE‐SF and WWE‐M regarding the rates of fetal loss (10.4% vs 6.7%, P = .255), major congenital malformations (8.5% vs. 11.1%, P = .395), and development quotient at 1 year of age <85 (42.5% vs 42.3%, P = .569) were not statistically significant. Compared to WWE‐PF, fewer WWE‐SF had AED dose escalation (14.9% vs 85.7%, P = .001) or increase in seizures (14.9% vs 100%, P = .001) during pregnancy. WWE‐SF had fewer infants with development quotient <85 (41.0% vs 100%, P = .005).

Significance

WWE‐SF can expect better control of seizures and decreased AED burden during pregnancy than WWE with focal epilepsies managed with medicines only. WWE who undergo surgery for epilepsy before their pregnancies can expect fewer seizures and lower AED burden during pregnancy.
Differential roles of miR‐15a/16‐1 and miR‐497/195 clusters in immune cell development and homeostasis
Authors: Hutter Katharina , Rülicke Thomas , Drach Mathias , Andersen Lill , Villunger Andreas , Herzog Sebastian
Published: July 2020

MicroRNAs (miRNAs) post‐transcriptionally repress almost all genes in mammals and thereby form an additional layer of gene regulation. As such, miRNAs impact on nearly every physiological process and have also been associated with cancer. Prominent examples of such miRNAs can be found in the miR‐15 family, composed of the bicistronic clusters miR‐15a/16‐1, miR‐15b/16‐2, and miR‐497/195. In particular, the miR‐15a/16‐1 cluster is deleted in almost two thirds of all chronic B lymphocytic leukemia (CLL) cases, a phenotype that is also recapitulated by miR‐15a/16‐1‐deficient as well as miR‐15b/16‐2‐deficient mice. Under physiological conditions, those two clusters have been implicated in T‐cell function, and B‐cell and natural killer (NK) cell development; however, it is unclear whether miR‐497 and miR‐195 confer similar roles in health and disease. Here, we have generated a conditional mouse model for tissue‐specific deletion of miR‐497 and miR‐195. While mice lacking miR‐15a/16‐1 in the hematopoietic compartment developed clear signs of CLL over time, aging mice deficient for miR‐497/195 did not show such a phenotype. Likewise, loss of miR‐15a/16‐1 impaired NK and early B‐cell development, whereas miR‐497/195 was dispensable for these processes. In fact, a detailed analysis of miR‐497/195‐deficient mice did not reveal any effect on steady‐state hematopoiesis or immune cell function. Unexpectedly, even whole‐body deletion of the cluster was well‐tolerated and had no obvious impact on embryonic development or healthy life span. Therefore, we postulate that the miR‐497/195 cluster is redundant to its paralog clusters or that its functional relevance is restricted to certain physiological and pathological conditions.
World cities and peripheral development: The interplay of gateways and subordinate places in Argentina and Ghana’s upstream oil and gas sector
Authors: Scholvin Sören
Published: July 2020

Serving as “gateways”, some world cities tie their wider hinterlands to global networks. The article revisits gateway–hinterland relations against the backdrop of assessments that lead to opposed conclusions on the benefits and shortcomings of integration into the world economy. Referring to the oil and gas sector in Argentina and Ghana, it answers the question of how gateways interact with subordinate places and also uncovers obstacles to peripheral development. The author finds that Accra and Buenos Aires concentrate corporate control. Argentina's capital serves as a gateway for knowledge generation and logistics too. Opportunities for peripheral development in both countries are considerable, albeit largely limited to generic services. Besides a certain concentration of business activities in the gateway cities, more important challenges to peripheral development are typical for small and medium enterprises (insufficient finance and management capabilities, unawareness of business opportunities, and the like). They include rent seeking and subcontracting. The latter leaves local companies in a particularly weak position vis‐à‐vis lead firms. The author argues that while integration into the world economy allows for peripheral development, the corresponding outcomes may not meet everyone's expectations. Related expectations must, therefore, be more down‐to‐earth than overly optimistic statements frequently made by politicians.
Small Area Estimation for Disease Prevalence Mapping
Authors: Wakefield Jonathan , Okonek Taylor , Pedersen Jon
Published: July 2020

Small area estimation (SAE) entails estimating characteristics of interest for domains, often geographical areas, in which there may be few or no samples available. SAE has a long history and a wide variety of methods have been suggested, from a bewildering range of philosophical standpoints. We describe design‐based and model‐based approaches and models that are specified at the area level and at the unit level, focusing on health applications and fully Bayesian spatial models. The use of auxiliary information is a key ingredient for successful inference when response data are sparse, and we discuss a number of approaches that allow the inclusion of covariate data. SAE for HIV prevalence, using data collected from a Demographic Health Survey in Malawi in 2015–2016, is used to illustrate a number of techniques. The potential use of SAE techniques for outcomes related to coronavirus disease 2019 is discussed.
Andrographolide attenuates epithelial‐mesenchymal transition induced by TGF‐β1 in alveolar epithelial cells
Authors: Li Jingpei , Liu Jun , Yue Weifeng , Xu Ke , Cai Weipeng , Cui Fei , Li Zhuoyi , Wang Wei , He Jianxing
Published: July 2020

Andrographolide (Andro), a component from Chinese medicinal herb Andrographis paniculata, could alleviate pulmonary fibrosis in rodents. Yet, whether and how Andro mitigates epithelial‐mesenchymal transition (EMT) induced by TGF‐β1 remain unknown. This study aimed to explore the effect of Andro on TGF‐β1‐induced EMT in human alveolar epithelial cells (AECs) and the mechanisms involved. We illustrated that Andro inhibited TGF‐β1‐induced EMT and EMT‐related transcription factors in alveolar epithelial A549 cells. Andro also reduced TGF‐β1‐induced cell migration and synthesis of pro‐fibrotic factors (ie CCN‐2, TGF‐β1), matrix metalloproteinases (ie MMP‐2, MMP‐9) and extracellular matrix (ECM) components (ie collagen 1), implying the inhibiting effect of Andro on TGF‐β1‐induced EMT‐like cell behaviours. Mechanistically, Andro treatment not only repressed TGF‐β1‐induced Smad2/3 phosphorylation and Smad4 nuclear translocation, but also suppressed TGF‐β1‐induced Erk1/2 phosphorylation and nuclear translocation in A549 cells. And treatment with ALK5 inhibitor (SB431542) or Erk1/2 inhibitors (SCH772984 and PD98059) remarkably reduced EMT evoked by TGF‐β1. In addition, Andro also reduced TGF‐β1‐induced intracellular ROS generation and NOX4 expression, and elevated antioxidant superoxide dismutase 2 (SOD2) expression, demonstrating the inhibiting effect of Andro on TGF‐β1‐induced oxidative stress, which is closely linked to EMT. Furthermore, Andro remarkably attenuated TGF‐β1‐induced down‐regulation of sirtuin1 (Sirt1) and forkhead box O3 (FOXO3), implying that Andro protects AECs from EMT partially by activating Sirt1/FOXO3‐mediated anti‐oxidative stress pathway. In conclusion, Andro represses TGF‐β1‐induced EMT in AECs by suppressing Smad2/3 and Erk1/2 signalling pathways and is also closely linked to the activation of sirt1/FOXO3‐mediated anti‐oxidative stress pathway.
Cytological analysis of integumentary and muscular adaptations in three sand‐dwelling marine teleosts, Ammodytes tobianus (Ammodytidae), Gorgasia preclara (Congridae) and Heteroconger hassi (Congridae) (Teleostei; Actinopterygii)
Authors: Canei Jérôme , Trupia Arnaud , Nonclercq Denis
Published: July 2020

Sandy bottoms are a ubiquitous environment found from sea bottoms to intertidal and freshwater zones. They are inhabited by many invertebrates and vertebrates which have developed morphological and physiological adaptations to sustain life under these particular conditions. Sandy habitats exhibit three potential constraints: abrasion, hypoxia and mechanical resistance. Here, three teleost species living in sandy environments were investigated: Ammodytes tobianus (Ammodytidae), Gorgasia preclara and Heteroconger hassi (Congridae). These teleost fishes were studied for their integument and muscular systems, which are potentially subject to sand abrasion and hypoxia, respectively. Based on histochemistry and transmission electron microscopy, we found the complex mucus system of G. preclara and H. hassi consists of two types of goblet cells and one type of sacciform cell. The secretions of both species are made of complex polysaccharides. In contrast, the scaly integument of A. tobianus has only a few goblet cells and no sacciform cells. We also highlighted, by immunohistochemistry, that the epidermal cell proliferation was much higher for this latter species, potentially resulting from the high rate of sand abrasion when A. tobianus buries itself quickly in the substrate. For all species, the major muscle fibre type was revealed by histoenzymology and corresponds to fast glycolytic fibres followed by intermediate fibres with slow fibres in the lowest proportion. Ammodytes tobianus possesses the highest fast fibre proportion (about 87% for A. tobianus and 75–78% for both garden eels). Our results provide new insights into the previously poorly studied teleost species, such as G. preclara, and allow us to highlight the complex skin histology of both garden eel species. Furthermore, the previously unknown muscle typing of these three species was determined.
Two‐Year Follow‐Up of the Efficacy of the PREP Training on Iranian Newlyweds
Authors: Fallahchai Reza , Fallahi Maryam , Badiee Manijeh
Published: July 2020

The aim of the present study was to replicate the efficacy of the Prevention and Relationship Education Program (PREP) training on marital satisfaction and dyadic adjustment among a group of Iranian newlyweds. One hundred and sixty heterosexual couples (N = 320 participants) were randomly assigned to an experimental or a wait list control group. Data from one hundred and forty‐eight couples were analyzed. Participants completed the ENRICH Marital Satisfaction Scale (The Family Journal, 1, 1993, 196–207) and Dyadic Adjustment Scale (The Journal of Sex Research, 39, 1976, 190–196) at pretest, posttest, 1‐year follow‐up, and 2‐year follow‐up. Results indicated that mean marital satisfaction and dyadic adjustment scores between the experimental and control groups were significantly different at posttest. Therefore, PREP training improved marital satisfaction and dyadic adjustment of couples at posttest. The data suggests that PREP training program can be introduced as an effective relationship education program for Iranian newlyweds.
Pentadactyl manus of the Metoposaurus krasiejowensis from the Late Triassic of Poland, the first record of pentadactyly among Temnospondyli
Authors: Konietzko‐Meier Dorota , Teschner Elżbieta M. , Bodzioch Adam , Sander P. Martin
Published: July 2020

Temnospondyli are commonly believed to have possessed four digits in the manus and five in the pes. However, actual finds of articulated autopodia are extremely rare. Therefore, an articulated, slightly incomplete forelimb skeleton with preserved manus of Metoposaurus krasiejowensis from the Late Triassic of Poland is important in providing new details about the structure and ossification sequence in the temnospondyl limb. The most important observation is the presence of five metacarpals in this specimen. This allows reconstructing the manus as pentadactyl. The number of phalanges and the distribution of distal articulation facets allow reconstruction of the digit formula as (2?)‐3‐3‐(3?)‐(2?). The well‐developed fifth digit suggests that the Metoposaurus manus shows a unique ossification sequence: the reduction or late ossification of the first digit conforms to the amniote‐frog pattern, and the early development of the second and third digit makes Metoposaurus similar to salamanders. Based on the distribution of pentadactyly vs. tetradactyly in the temnospondyl manus, the number of digits was not phylogenetically constrained in temnospondyls, similar to today's amphibians.
Ultrasound Detection of Vagus Nerve Atrophy in Bulbar Amyotrophic Lateral Sclerosis
Authors: Holzapfel Korbinian , Naumann Markus
Published: July 2020

BACKGROUND AND PURPOSE

Neuromuscular ultrasound in amyotrophic lateral sclerosis (ALS) is of increasing interest. As bulbar symptoms are commonly developed by most ALS patients during disease, the aim of our study was to find possible sonographic changes of vagus nerve size in bulbar affected ALS patients.

METHODS

We investigated 24 ALS patients and 19 controls without neuromuscular disorders. In ALS patients, bulbar affection was documented clinically (eg, dysarthria, dysphagia, and fasciculations) or subclinically using ultrasound and electromyography of bulbar muscles. Vagus nerve ultrasound was performed in all participants bilaterally at the level of the thyroid gland.

RESULTS

The cross‐sectional area (CSA) of the vagus nerve in bulbar affected ALS patients (mean CSA right/left 1.9 ± .7 mm²/1.8 ± .6 mm²) was significantly reduced on both sides compared to controls (mean CSA right/left 2.2 ± .6 mm²/2.0 ± .3 mm²) – right: P = .0387, left: P = .0386. Receiver operating characteristic curve analysis of the vagus nerve CSA yielded a sensitivity of 66.7% and a specificity of 63.2% (cutoff value 1.85 mm²). Vagus nerve CSA did not correlate significantly with age in controls (right: P = .45, left: P = .66). In controls and ALS patients, there was no significant difference of vagus nerve CSA between the right and left sides (controls: P = .43; patients: P = .86).

CONCLUSION

Our study demonstrates vagus nerve atrophy in bulbar affected ALS patients. Further studies are warranted investigating the relevance of our finding for monitoring disease progression in ALS.
Gender at Work Across Nations: Men and Women Working in Male‐Dominated and Female‐Dominated Occupations are Differentially Associated with Agency and Communion
Authors: Froehlich Laura , Olsson Maria I. T. , Dorrough Angela R. , Martiny Sarah E.
Published: July 2020

Occupational gender segregation is a worldwide phenomenon. Research from Western regions such as the United States and Europe shows that the observation of occupational gender segregation can perpetuate gender stereotypes (social role theory; men are ascribed agentic traits, whereas women are ascribed communal traits). However, predictions from social role theory have not been well‐tested in non‐Western nations. In a study with 1,918 participants from 10 nations systematically differing in gender inequality, we investigated the extent to which target men and women in gender‐segregated occupations are associated with stereotype‐relevant traits. Results showed that 12 preselected occupations were perceived as gender‐segregated in all nations. In line with social role theory, across nations, target men and women in male‐dominated occupations were associated with agentic traits, whereas targets in female‐dominated occupations were associated with communal traits. Targets’ gender, but not national‐level gender inequality, moderated these results. The relevance of cross‐national research for understanding gender stereotypes and pathways to reduce gender inequality are discussed.
Effectiveness of direct‐acting agents for chronic hepatitis C treatment in South America: A systematic review and meta‐analysis
Authors: Castro Filho Elio C. , Piedade Juliana , Castro Rodolfo , Luz Paula M. , Fernandes Flavia , Grinsztejn Beatriz , Veloso Valdilea G. , Pereira Gustavo Henrique , Perazzo Hugo
Published: July 2020

The effectiveness of direct‐acting agents (DAAs) for hepatitis C treatment in limited‐resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12‐week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention‐to‐treat (ITT) and per‐protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random‐effects model (DerSimonian‐Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co‐infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South‐American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2‐94.7] and 95.5% [94.3‐96.6] by ITT (11 studies; n = 4,153; I2 = 84.2%) and per‐protocol analysis (15 studies; n = 4,833; I2 = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co‐infection [4 studies; RR = 1.03 (0.99‐1.07)] and those naive compared with treatment experimented‐individuals [9 studies; RR = 1.01 (1.00‐1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02‐1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited‐resource settings to decrease the burden of liver disease in HCV‐infected patients. PROSPERO[CRD 42019134603].