bluuebunny/crossref_metadata_2025 huggingface dataset:
A disaster diplomacy perspective of acute public health events
Authors: Whittaker Charlie , Frühauf Anna , Burthem Samuel John , Parry Rebecca Shoshanah , Kotikalapudi Meghana , Liang Yihui , Barker Mary Moffett , Patel Parth Rohit , Kelman Ilan
Published: August 2018

Conceptions of acute public health events typically assume that they are tackled exclusively or principally through technical and medical solutions. Yet health and politics are inexorably linked. To better understand this link, this paper adopts a disaster diplomacy perspective for analysing and assessing the impacts of acute public health events on diplomatic outcomes. Two gaps in understanding disaster‐health‐politics connections are addressed: (i) how health interventions can impact diplomatic endeavours, especially for (ii) acute public health events. Three diverse case studies are interpreted from a disaster diplomacy perspective: Cuba's medical diplomacy, China and Severe Acute Respiratory Syndrome (SARS), and polio vaccination. Disaster diplomacy permits deeper investigation and analysis of connections amongst health, disaster, and diplomatic activities by viewing efforts on acute public health events as being political through disaster risk reduction (beforehand) and disaster response (during and afterwards). Understanding improves how health interventions affect diplomacy and on disaster diplomacy's limitations.
Epigenetics of fragile X syndrome and fragile X‐related disorders
Authors: Kraan Claudine M , Godler David E , Amor David J
Published: August 2018

The fragile X mental retardation 1 gene (FMR1)‐related disorder fragile X syndrome (FXS) is the most common heritable form of cognitive impairment and the second most common cause of comorbid autism.FXSusually results when a premutation trinucleotideCGGrepeat in the 5′ untranslated region of theFMR1gene (CGG55–200) expands over generations to a full mutation allele (CGG>200). This expansion is associated with silencing of theFMR1promoter via an epigenetic mechanism that involvesDNAmethylation of theCGGrepeat and the surrounding regulatory regions. Decrease inFMR1transcription is associated with loss of theFMR1protein that is needed for typical brain development. The past decade has seen major advances in our understanding of the genetic and epigenetic processes that underlieFXS. Here we review these advances and their implications for diagnosis and treatment for individuals who haveFMR1‐related disorders.

What This Paper Adds

Improved analysis of DNA methylation allows better epigenetic evaluation of the fragile X gene.

New testing techniques have unmasked interindividual variation among children with fragile X syndrome.

New testing methods have also detected additional cases of fragile X.
Altered frequency of Th17 and Treg cells in new‐onset systemic lupus erythematosus patients
Authors: Chen Min , Chen Xiaoqi , Wan Qianqian
Published: August 2018

Background

T helper 17 (Th17) and regulatory T (Treg) cells play an important role in pathogenesis of systemic lupus erythematosus (SLE). Their imbalance was reported in treated SLE patients, while very little is known about the relationship between Th17 and Treg cells in new‐onset untreated SLE patients.

Aim

To assess the role of Th17/Treg cells in the pathogenesis of new‐onset SLE.

Materials and methods

Thirty‐nine new‐onset SLE patients and 33 age‐matched healthy adults were enrolled. We analysed Th17 and Treg cells in different level, including their frequencies in peripheral blood mononuclear cell, the expression of interleukin‐17 A (IL‐17A) and forkhead box P3 (FoxP3) proteins, the expression of retinoid‐related orphan nuclear receptor γt (RORγt) and FoxP3 genes and plasma level of IL‐17A.

Results

The frequency of Th17 and Treg cells, the expression of IL‐17A among Th17 cell, the plasma level of IL‐17A, the expression of RORγt and FoxP3 genes were all significantly higher in SLE patients. Th17 cells were negatively correlated with Treg cells. We also found that plasma level of IL‐17A was positively correlated with SLE disease activities index (SLEDAI) scores and an equation among the level of C3, IgA, IL‐17A and SLEDAI scores.

Conclusions

Results indicate that Th17 and Treg cells take roles in the pathogenesis of SLE. Th17 cells might suppress the differentiation of Treg cells, and feedback effects might exist between them during SLE pathogenesis. The measure of plasma level of IL‐17A may be useful for evaluation of disease activity in new‐onset SLE patients.
Occupational Choice with Endogenous Spillovers
Authors: Albornoz Facundo , Cabrales Antonio , Hauk Esther
Published: August 2018

We study a model that integrates productive and socialising efforts with occupational choice, and endogenous spillovers. We show that more talented individuals work harder and contribute more to externalities, but also have incentives to segregate. Average socialising increases the productivity of the occupation. The size of an occupation grows with its synergies. Individuals underinvest in productive and socialising effort, and sort themselves inefficiently into occupations. We derive the optimal subsidy for sorting into different occupations. Finally, we derive a rule to identify overpopulated sectors and establish the connection between inequality of talents, socialising, productive efforts and occupation size.
Canker and fine‐root loss of Malus sieversii (Ldb.) Roem. caused by Phytophthora plurivora in Xinjiang Province in China
Authors: Liu Ai‐Hua , Shang Jing , Zhang Jing‐Wen , Kong Ting‐Ting , Yue Zhao‐Yang , Wen Jun‐Bao
Published: August 2018

In recent years, the distribution and population of the Xinjiang wild apple, Malus sieversii, a protected vulnerable plant among endangered rare germplasm resources of China, have been decreasing. A field survey conducted during 2015–2017 detected decline and dieback of Xinjiang wild apple in the Yili region in Xinjiang Province. Two Phytophthora spp. were isolated from cankers and soil samples around symptomatic M. sieversii trees: One isolate was shown to cause infection, based on Koch's postulates. The isolate was identified as Phytophthora plurivora based on morphological features, physiological characteristics, ITS1–5.8S–ITS2 rDNA and cox1 sequence analyses. This is the first report of P. plurivora pathogenicity on Xinjiang wild apple in Xinjiang Province in China, constituting a new host for this pathogen. The potential of P. plurivora to cause damage in pure stands of Xinjiang wild apple in Xinjiang Province should be determined.
First report of Apoharknessia eucalyptorum on Eucalyptus dunnii in Brazil
Authors: de Almeida Garrett Alexandre Techy , Imani Jafargholi , Tambarussi Evandro Vagner , de Oliveira Garcia Flávio Augusto , Kogel Karl‐Heinz , Figueiredo Filho Afonso
Published: August 2018

Herein, we describe the conidia and phylogeny of Apoharknessia eucalyptorum, a causal agent of leaf blight, and the symptoms of infection on eucalypt trees, which is the first report of A. eucalyptorum in Brazil. Inoculation tests and re‐isolation of A. eucalyptorum confirmed that Eucalyptus dunnii is a host for this leaf blight. Because the known distribution of A. eucalyptorum is limited, no analysis of the impacts of the disease on tree growth has been conducted, and more detailed studies are needed on the aetiology and epidemiology of this leaf disease.
Adopting a new technology: potatoes and population growth in the periphery
Authors: Berger Thor
Published: August 2018

Sweden's population doubled in size between 1750 and 1850 despite a century of stagnating per capita incomes and real wages, which has led many historians to attribute the population explosion to the introduction of the potato. This article provides the first systematic evidence on the potato's contribution to Swedish living standards and population growth. Potatoes at least doubled output per acre, and welfare ratios that account for potato consumption imply that they raised living standards significantly for labourers. Estimates that exploit regional differences in the suitability of land for cultivating potatoes further show that cities, counties, and rural parishes with more land suitable for potato cultivation experienced a sharp relative acceleration in population growth as the potato spread in the early nineteenth century. An expansion of the population was mainly driven by relative increases in fertility and, consistent with Malthusian predictions, there was no long‐run impact on per capita incomes. According to these estimates, the introduction and spread of the potato can account for one‐tenth of population growth between 1800 and 1850, thus suggesting that it was an important catalyst for the Swedish population explosion.
Experiences during the execution of emergency endodontic treatment and levels of anxiety in dental students
Authors: Grock Camila Hélen , Luz Luciana Batista , Oliveira Vanessa Farias , Ardenghi Thiago Machado , Bizarro Lisiane , Ferreira Maria Beatriz Cardoso , Montagner Francisco
Published: August 2018

Purpose

This study aims to evaluate the experience of dental students and assess their anxiety levels when performing emergency endodontic treatments.

Methods

Undergraduate students completed the STAI‐Trait/State and a questionnaire to assess their confidence level to perform each step of an emergency endodontic procedure. They also answered a numerical scale (NRS) for anxiety before and after emergency care. Ten randomly selected students from the same sample further participated in a focus group aimed at obtaining qualitative data on their perception of endodontic treatments’ conduction and the learning process necessary to perform them.

Results

A total of 23 students joined the study. The majority of the participants reported feeling “confident” when performing local anaesthesia (57.6%), rubber dam placement (57.6%) and coronal sealing (72.7%). However, a small number reported feeling “little confident” to perform access cavity (15.2%) or pulpotomy/pulpectomy (24.2%). Students who scored above the 3rd quartile of STAI‐Trait/State were classified as “highly anxious,” and comprised 26.1% of the sample. The values of NRS scale were higher in the preoperative when compared with the post‐operative assessment. All students classified as “highly anxious” reported low confidence in performing “access cavity” and “pulpotomy/pulpectomy.”

Conclusion

Both quantitative and qualitative analysis showed different anxiety levels in dental students. It can possibly contribute to a reduction in confidence prior to emergency endodontic procedures. The current findings suggest it might be important to rearrange activities in order to allow for more practical classes in Endodontics.
Truancy in Europe: Does the type of educational system matter?
Authors: Keppens Gil , Spruyt Bram
Published: August 2018

Truancy is known to: Hamper academic achievement, predict a range of school‐related problems and cause early school leaving. Hence, the development and implementation of measures to tackle truancy are considered as important strategies to prevent early school leaving in Europe. Despite this, there is almost no comparative research which studies variation in truancy rates. This article relies on PISA 2012 data from 24 European countries to empirically answer two questions: (1) To what degree do truancy rates vary cross‐nationally? and (2) Do these differences in truancy rates relate to characteristics of the educational system? We found that between‐country truancy rates varied more than differences in early school leaving. Moreover, even after taking into account control variables such as economic development and youth unemployment rates, the ways in which educational systems select and group pupils are closely related to truancy rates.
Children's rights and their subjective well‐being from a multinational perspective
Authors: Casas Ferran , González‐Carrasco Mònica , Luna Xevi
Published: August 2018

This article explores the relationship between children's knowledge and perceptions about their rights and subjective well‐being (SWB) in a sample of 8‐, 10‐ and 12‐year‐olds in 18 countries, taking account of gender differences. Children's knowledge and perceptions about their rights were analysed considering whether they reported that they knew their rights, whether they had heard about the UN Convention on the Rights of the Child (CRC) and whether they thought that, in their country, adults respected their rights. To explore SWB, a modified version of the Student's Life Satisfaction Scale, adapted by the Children's Worlds project, was used. Children reporting that they knew their rights, knew about the CRC, or thought that in their country adults respected their rights demonstrated significantly higher SWB scores than those reporting otherwise in the 18 countries. The effects of perceiving that adults in general respected children's rights in their own country on SWB were much more important than the knowledge of children's rights or the knowledge of the CRC. Results provide useful indications on how to promote children's well‐being in public policies, including in education, through the promotion of their rights.
The impact of EU‐funded development interventions on teaching practices in Hungarian schools
Authors: Fazekas Ágnes
Published: August 2018

This article analyses the impact of EU‐funded curriculum development interventions implemented in Hungary between 2004 and 2012, focusing on contextual features influencing school‐ and teacher‐level adoption processes. It is based on a four‐year empirical study which aimed at better understanding the impact mechanisms of modernising interventions targeted at school and classroom level teaching practices. The results show that: (1) EU‐funded curriculum development programmes have had a significant impact on a large number of Hungarian schools (ISCED 1, 2 and 3), (2) interventions were particularly effective in schools operating as knowledge‐intensive organisations and (3) the impact of interventions was influenced by the specificities of both the programme and the local context of adoption. The first part of the article presents the theoretical framework of the research and the main characteristics of EU‐funded curriculum‐development programmes. The following section explores the key features of the research, including its purpose, design and survey instruments. The last part presents the main outcomes, showing the measured impact of interventions on everyday practices of both schools as organisations and individual teachers, as well as the possible links between organisational characteristics and the success of programme implementation.
Combined effects of nitrogen fertilizer and straw application on aggregate distribution and aggregate‐associated organic carbon stability in an alkaline sandy loam soil
Authors: Wang Z. , Wang Z. , Ma L. J. , Ali Khattak W. , Hu W. , Meng Y. L. , Zhou Z. G.
Published: August 2018

Research on aggregate‐associated organic carbon (AOC) stability has increased, but its response to nitrogen (N) and straw (S) application after nitrogen reduction in alkaline sandy loam soil remains unclear. A 2‐year field study and a short‐term incubation experiment were performed to investigate the combined effect of the N + S application on aggregate distribution and stability, and AOC content and mineralization in eastern China. The study involved three N amounts (75, 150 and 300 kg N ha−1) with or without straw amendments under continuous cotton–barley rotation. The N + S application promoted the formation of larger macroaggregates (8–2 mm), with larger mean weight diameter and geometric mean diameter than with N application alone. Aggregate stability increased significantly with increasing rate of N application. The amount of N had less effect on AOC content in the 0–20‐cm layer and cumulative mineralization of AOC in both layers compared with the N + S application. The addition of straw in promoting AOC, however, was more evident in the 20–40‐cm layer. Compared with N fertilizer alone, applying N + S increased the cumulative mineralization of AOC by 27.7% in the 0–20‐cm layer and by 80.9% in the 20–40‐cm layer for different rates of N and aggregate sizes. In addition, at 0–20‐cm depth, there was less C mineralization in macroaggregates than in microaggregates, indicating that macroaggregates showed better protection of AOC in that layer. Our study suggests that N application alone had a large effect on aggregate stability, whereas combined N + S application had a large effect on AOC content and its mineralization in the soil studied.

Highlights

We studied aggregate and aggregate‐associated organic carbon stability under N and straw application in alkaline sandy loam soil.

Nitrogen and straw treatment carried out with prior application of a gradient of excessively large N inputs.

Macroaggregates showed better protection of AOC in the 0–20‐cm soil layer.

N and N + S applications had large effects on aggregate stability, AOC content and its mineralization.
Elevated atmospheric concentrations of carbon dioxide reduce monarch tolerance and increase parasite virulence by altering the medicinal properties of milkweeds
Authors: Decker Leslie E. , de Roode Jacobus C. , Hunter Mark D.
Published: August 2018

Hosts combat their parasites using mechanisms of resistance and tolerance, which together determine parasite virulence. Environmental factors, including diet, mediate the impact of parasites on hosts, with diet providing nutritional and medicinal properties. Here, we present the first evidence that ongoing environmental change decreases host tolerance and increases parasite virulence through a loss of dietary medicinal quality. Monarch butterflies use dietary toxins (cardenolides) to reduce the deleterious impacts of a protozoan parasite. We fed monarch larvae foliage from four milkweed species grown under either elevated or ambient CO2, and measured changes in resistance, tolerance, and virulence. The most high‐cardenolide milkweed species lost its medicinal properties under elevated CO2; monarch tolerance to infection decreased, and parasite virulence increased. Declines in medicinal quality were associated with declines in foliar concentrations of lipophilic cardenolides. Our results emphasize that global environmental change may influence parasite–host interactions through changes in the medicinal properties of plants.
Phosphatase activity and nitrogen fixation reflect species differences, not nutrient trading or nutrient balance, across tropical rainforest trees
Authors: Batterman Sarah A. , Hall Jefferson S. , Turner Benjamin L. , Hedin Lars O. , LaHaela Walter J. Kimiko , Sheldon Pete , van Breugel Michiel
Published: August 2018

A fundamental biogeochemical paradox is that nitrogen‐rich tropical forests contain abundant nitrogen‐fixing trees, which support a globally significant tropical carbon sink. One explanation for this pattern holds that nitrogen‐fixing trees can overcome phosphorus limitation in tropical forests by synthesizing phosphatase enzymes to acquire soil organic phosphorus, but empirical evidence remains scarce. We evaluated whether nitrogen fixation and phosphatase activity are linked across 97 trees from seven species, and tested two hypotheses for explaining investment in nutrient strategies: trading nitrogen‐for‐phosphorus or balancing nutrient demand. Both strategies varied across species but were not explained by nitrogen‐for‐phosphorus trading or nutrient balance. This indicates that (1) studies of these nutrient strategies require broad sampling within and across species, (2) factors other than nutrient trading must be invoked to resolve the paradox of tropical nitrogen fixation, and (3) nitrogen‐fixing trees cannot provide a positive nitrogen‐phosphorus‐carbon feedback to alleviate nutrient limitation of the tropical carbon sink.
Variation between individuals fosters regional species coexistence
Authors: Uriarte María , Menge Duncan
Published: August 2018

Although individual‐level variation (IV) is ubiquitous in nature, it is not clear how it influences species coexistence. Theory predicts that IV will hinder coexistence but empirical studies have shown that it can facilitate, inhibit, or have a neutral effect. We use a theoretical model to explore the consequences of IV on local and regional species coexistence in the context of spatial environmental structure. Our results show that individual variation can have a positive effect on species coexistence and that this effect will critically depend on the spatial structure of such variation. IV facilitates coexistence when a negative, concave‐up relationship between individuals’ competitive response and population growth rates propagates to a disproportionate advantage for the inferior competitor, provided that each species specialises in a habitat. While greater variation in the preferred habitat generally fosters coexistence, the opposite is true for non‐preferred habitats. Our results reconcile theory with empirical findings.
Abnormal hippocampal functional network and related memory impairment in pilocarpine‐treated rats
Authors: Jiang Yin , Han Chun‐Lei , Liu Huan‐Guang , Wang Xiu , Zhang Xin , Meng Fan‐Gang , Zhang Jian‐Guo
Published: August 2018

Objective

Although abnormal hippocampal structure and impaired spatial memory have been revealed in a pilocarpine rat model of temporal lobe epilepsy (TLE), the brain functional network changes are still unclear. The aim of the present study was to investigate the changes of brain functional connectivity related to the hippocampus and the associated memory impairment in a pilocarpine model of TLE.

Methods

Functional magnetic resonance imaging signals were recorded in pilocarpine‐treated rats and controls by using a 7.0 T magnetic resonance scanner, and independent component analysis was performed to determine the hippocampal functional network. Behavioral tests, including novel location test, novel object test, and episodic memory test, were utilized to evaluate different aspects of memory impairment.

Results

Memory impairment was observed in the TLE group in all three behavior tests. As compared to control, decreased connectivity of the hippocampal functional network was observed in the anterior dorsal hippocampus, the amygdala, the thalamus, the motor cortex, and the somatosensory cortex in the TLE group. Meanwhile, increased connectivity was found in the visual cortex, the mesencephalon, and the insula in the TLE group. Correlation analysis revealed that functional connections between the hippocampal network and brain regions such as the dorsal hippocampus and the thalamus specifically relate to the spatial memory behavior, whereas connections between the hippocampal network and regions such as the amygdala, the motor cortex, the somatosensory cortex, and the mesencephalon relate to both the spatial and the object memory performance.

Significance

Our results indicated a trend of decreased connectivity in the hippocampal functional network, as well as spatial, object, and episodic memory impairment in the pilocarpine‐induced TLE rat. Moreover, connections within the hippocampal network showed a relationship with spatial memory, and connections between the hippocampal network and regions in other networks revealed an association with both spatial and object memory.
Color polarization vision mediates the strength of an evolutionary trap
Authors: Robertson Bruce A. , Horváth Gábor
Published: August 2018

Evolutionary traps are scenarios in which animals are fooled by rapidly changing conditions into preferring poor‐quality resources over those that better improve survival and reproductive success. The maladaptive attraction of aquatic insects to artificial sources of horizontally polarized light (e.g., glass buildings, asphalt roads) has become a first model system by which scientists can investigate the behavioral mechanisms that cause traps to occur. We employ this field‐based system to experimentally investigate (a) in which portion(s) of the spectrum are polarizationally water‐imitating reflectors attractive to nocturnal terrestrial and aquatics insects, and (b) which modern lamp types result in greater attraction in this typical kind of nocturnal polarized light pollution. We found that most aquatic taxa exhibited preferences for lamps based upon their color spectra, most having lowest preference for lamps emitting blue and red light. Yet, despite previously established preference for higher degrees of polarization of reflected light, most aquatic insect families were attracted to traps based upon their unpolarized spectrum. Chironomid midges, alone, showed a preference for the color of lamplight in both the horizontally polarized and unpolarized spectra indicating only this family has evolved to use light in this color range as a source of information to guide its nocturnal habitat selection. These results demonstrate that the color of artificial lighting can exacerbate or reduce its attractiveness to aquatic insects, but that the strength of attractiveness of nocturnal evolutionary traps, and so their demographic consequences, is primarily driven by unpolarized light pollution. This focuses management attention on limiting broad‐spectrum light pollution, as well as its intentional deployment to attract insects back to natural habitats.
A Culturally Adapted Intervention for Mexican‐Origin Parents of Adolescents: The Need to Overtly Address Culture and Discrimination in Evidence‐Based Practice
Authors: Parra‐Cardona Rubén , López‐Zerón Gabriela , Leija Silvia Gisela , Maas Megan K. , Villa Monica , Zamudio Efraín , Arredondo Melecia , Yeh Hsueh‐Han , Domenech Rodríguez Melanie M.
Published: August 2018

Latino/a populations in the United States are negatively impacted by widespread mental health disparities. Although the dissemination of culturally relevant parent training (PT) programs constitutes an alternative to address this problem, there is a limited number of efficacious culturally adapted PT prevention interventions for low‐income Latino/a immigrant families with adolescents. The current manuscript describes the level of acceptability of a version of the GenerationPMTO® intervention adapted for Latino/a immigrant families, with an explicit focus on immigration‐related challenges, discrimination, and promotion of biculturalism. Qualitative reports were provided by 39 immigrant parents who successfully completed the prevention parenting program. The majority of these parents self‐identified as Mexican‐origin. According to qualitative findings, participants reported overall high satisfaction with immigration and culture‐specific components. Parents also expressed high satisfaction with the core GenerationPMTO parenting components and provided specific recommendations for improving the intervention. Current findings indicate the need to adhere to the core components that account for the effectiveness of PT interventions. Equally important is to thoroughly adapt PT interventions according to the cultural values and experiences that are relevant to target populations, as well as to overtly address experiences of discrimination that negatively impact underserved Mexican‐origin immigrant families. Due to the exploratory nature of this study, the efficacy and effectiveness of the adapted prevention intervention remains to be established in empirical research.
QT length during methadone maintenance treatment: gene × dose interaction
Authors: Zerdazi El‐Hadi , Vorspan Florence , Marees Andries T. , Naccache François , Lepine Jean‐Pierre , Laplanche Jean‐Louis , Prince Nathalie , Marie‐Claire Cynthia , Bellivier Frank , Mouly Stéphane , Bloch Vanessa
Published: August 2018

Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. For other medical conditions, QTc lengthening has been described as the result of interactions between pharmacological treatments and genetic factors. Former heroin‐dependent subjects under methadone maintenance treatment in remission for at last 3 months were recruited. We studied the association between QTc length (Bazett formula) and 126 SNPs located on five genes (KCNE1, KCNQ1, KCNH2, NOS1AP and SCN5A) previously associated with drug‐induced QT prolongation. Both SNP‐based and gene‐based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length. In our sample of 154 patients, current methadone daily dose was associated with QTc length (rPearson = 0.26; P = 10−3). Only one SNP, rs11911509 on KCNE1, remained significantly associated with QT length after correction for multiple testing (P = 3.84 × 10−4; pcorrected = 0.049). Using a gene‐based approach, KCNE1 was also significantly associated with QTc length (pempirical = 0.02). We found a significant interaction between methadone dosage and rs11911509 minor allele count (allele A vs. C; P = 0.01). Stratified analysis revealed that the correlation between QTc length and methadone dosage was restricted only to AA carriers of this top SNP. Patients’ genetic background should be taken into account in the case of clinically relevant QT enlargement during methadone maintenance treatment.
Efficient SSA‐mediated precise genome editing using CRISPR/Cas9
Authors: Li Xinyi , Bai Yichun , Cheng Xinzhen , Kalds Peter Girgis Tawfek , Sun Bing , Wu Yun , Lv Huijiao , Xu Kun , Zhang Zhiying
Published: August 2018

CRISPR/Cas9 has been emerging as a main player in genome editing field since its advent. However, CRISPR/Cas9‐induced precise gene editing remains challenging since it requires no scar left after editing. Among the few reports regarding two‐step ‘pop in & out’ technologies for precise gene editing, the combination of CRISPR/Cas9 with Cre/LoxP demonstrates a higher efficiency, but leaves behind a 34‐base pair of tag sequence due to its inherent property. Another method utilizes piggyBac transposon for removing the selection cassette, and its disadvantage is the difficulty in controlling its random reintegration after releasing. Here, we report a novel two‐step precise gene‐editing method by leveraging the SSA‐mediated repair mechanism into the CRISPR/Cas9‐mediated gene‐editing system. An integrating cassette was developed with positive and negative selection markers, which was flanked by direct repeat sequences with desired mutations as SSA arms. After the targeted integration of the cassette mediated by CRISPR/Cas9‐induced homologous‐directed repair, cell clones were first selected through the positive selection. In the second round targeting, the selection cassette was removed by the SSA‐mediated DNA double‐strand break (DSB) repair without any scar left behind. The novel seamless genome editing technique was tested on CCR5 and APP loci, and finally demonstrated, respectively, up to 45.83% and 68% of precise genome editing efficiency. This study provides a new efficient approach for precise genome editing and gene correction.
Size of Financing Need and the Choice between Asset Sales and Security Issuances
Authors: Desai Chintal A. , Gupta Manu
Published: August 2018

We study the effect of the size of financing need on a firm's choice between selling assets and issuing securities to finance its investments. The balance sheet effect predicts that a firm prefers to sell assets when the financing need is relatively small as there is less information asymmetry regarding the value of a (small) subset of its assets. When the financing need is large, a firm prefers issuing securities to selling assets. We find evidence supporting the prediction. Our findings remain unchanged when we employ measures of financing need that are relatively independent of the actual amount of financing raised.
Climate variability and sardine recruitment in the California Current: A mechanistic analysis of an ecosystem model
Authors: Politikos Dimitrios V. , Curchitser Enrique N. , Rose Kenneth A. , Checkley David M. , Fiechter Jerome
Published: August 2018

Recruitment varies substantially in small pelagic fish populations. Understanding of the mechanisms linking environment to recruitment is essential for the effective management of fisheries resources. In this study, we used a fully coupled end‐to‐end ecosystem model to study the effect of climate variability on sardine recruitment in the California Current System during 1965–2006. Ocean variability was represented by ROMS hydrodynamic and NEMURO biogeochemical models, and sardine population dynamics was simulated through a full life cycle individual‐based model. Model analysis was designed to elucidate how changes in abiotic and biotic conditions may impact the spawning habitats, early life stage survival, and ultimately recruitment of sardine. Our findings revealed the importance of spatial processes to shape early life stages dynamics. Shifts in spawning habitats were dictated by the spatial variations in temperature and the behavioral movement of adults. Additionally, the spatial match of eggs with warmer temperatures and larvae with their prey influenced their survival. The northward shifts in spawning locations and the accomplishment of good recruitment in warmer years agreed with existing knowledge. Egg production and survival during egg and yolk‐sac larval stages were key factors to drive the long‐term variations in recruitment. Finally, our analysis provided a quantitative assessment of climate impact on year‐to‐year variation in sardine recruitment by integrating multiple hypotheses.
Decoding the transcriptional programs activated by psychotropic drugs in the brain
Authors: Zygmunt Magdalena , Piechota Marcin , Rodriguez Parkitna Jan , Korostyński Michał
Published: August 2018

Analysis of drug‐induced gene expression in the brain has long held the promise of revealing the molecular mechanisms of drug actions as well as predicting their long‐term clinical efficacy. However, despite some successes, this promise has yet to be fulfilled. Here, we present an overview of the current state of understanding of drug‐induced gene expression in the brain and consider the obstacles to achieving a robust prediction of the properties of psychoactive compounds based on gene expression profiles. We begin with a comprehensive overview of the mechanisms controlling drug‐inducible transcription and the complexity resulting from expression of noncoding RNAs and alternative gene isoforms. Particular interest is placed on studies that examine the associations within drug classes with regard to the effects on gene transcription, alterations in cell signaling and neuropharmacological drug properties. While the ability of gene expression signatures to distinguish specific clinical classes of psychotropic and addictive drugs remains unclear, some reports show that under specific constraints, drug properties can be predicted based on gene expression. Such signatures offer a simple and effective way to classify psychotropic drugs and screen novel psychoactive compounds. Finally, we note that the amount of data regarding molecular programs activated in the brain by drug treatment has grown exponentially in recent years and that future advances may therefore come in large part from integrating the currently available high‐throughput data sets.
Normal peripheral circadian phase in the old‐old with abnormal circadian behavior
Authors: Yamaguchi Ai , Tatsumoto Muneto , Matsumura Ritsuko , Endo Takuyuki , Hirata Koichi , Tokuda Isao , Akashi Makoto
Published: August 2018

Almost all organisms maintain a circadian clock from birth to death to synchronize their own physiology and behavior with the earth's rotation. However, extensive studies based on animal experiments have showed that aging results in circadian dysfunction. Human studies have also indicated age‐associated abnormal phase, reduced amplitude and enhanced fragmentation in circadian physiology and behavior, thereby strongly implying age‐related dysfunction of the clock machinery. Here, we carried out functional assessment of the circadian clock machinery in elderly patients aged 83–94 with severe dementia who showed abnormal circadian behavior. To investigate whether or not the systemic pathway from the circadian input to peripheral clocks functioned normally, the circadian phase in peripheral clock gene expression rhythms was evaluated using plucked hair tissues. Unexpectedly, the phase in all volunteer patients was within a range similar to that of healthy subjects. The circadian pathway from external inputs to peripheral clocks may therefore function normally, even in the old‐old with severe dementia.
Groundwater Pumping Is a Significant Unrecognized Contributor to Global Anthropogenic Element Cycles
Authors: Stahl Mason O.
Published: August 2018

Quantifying anthropogenic contributions to elemental cycles provides useful information regarding the flow of elements important to industrial and agricultural development and is key to understanding the environmental impacts of human activity. In particular, when anthropogenic fluxes reach levels large enough to influence an element's overall cycle the risk of adverse environmental impacts rises. While intensive groundwater pumping has been observed to affect a wide‐range of environmental processes, the role of intensive groundwater extraction on global anthropogenic element cycles has not yet been characterized. Relying on comprehensive datasets of groundwater and produced water (groundwater pumped during oil/gas extraction) chemistry from the U.S. Geological Survey along with estimates of global groundwater usage, I estimate elemental fluxes from global pumping, consumptive use, and depletion of groundwater. I find that groundwater fluxes appreciably contribute to a number of elements overall cycles and thus these cycles were underestimated in prior studies, which did not recognize groundwater pumping's role. I also estimate elemental loadings to agricultural soils in the United States and find that in some regions, groundwater may provide a significant portion (more than 10%) of crop requirements of key nutrients (K, N). With nearly 40% of globally irrigated land under groundwater irrigation, characterizing nutrient and toxic element fluxes to these soils, which ultimately influence crop yields, is important to our understanding of agricultural production. Thus, this study improves our basic understanding of anthropogenic elemental cycles and demonstrates that quantification of groundwater pumping elemental fluxes provides valuable information about the potential for environmental impacts from groundwater pumping.
Patient involvement in qualitative data analysis in a trial of a patient‐centred intervention: Reconciling lay knowledge and scientific method
Authors: Frost Julia , Gibson Andy , Harris‐Golesworthy Faith , Harris Jim , Britten Nicky
Published: August 2018

Background

We conducted a pilot study of an intervention to facilitate patients’ agenda setting in clinical consultations. The primary aim of the study was to test the feasibility of running the randomized controlled trial. A secondary objective was to assess the extent to which patient and public involvement (PPI) could contribute to the process of qualitative data analysis (QDA).

Aims

To describe a novel approach to including patient partners in QDA; to illustrate the kinds of contribution that patient partners made to QDA in this context; and to propose a characterization of a process by which patient involvement can contribute to knowledge production.

Methods

Six patient and public representatives were supported to contribute to data analysis via a range of modalities. During a series of QDA workshops, experienced research staff role‐played consultations and interviews, and provided vignettes. Workshop data and PPI diaries were analysed using thematic discourse analysis.

Results

We characterized a process of thesis, antithesis and synthesis. This PPI group contributed to the rigour and validity of the study findings by challenging their own and the researchers’ assumptions, and by testing the emerging hypotheses. By training PPI representatives to undertake qualitative data analysis, we transformed our understanding of doctor–patient consultations.

Conclusions

This research required changes to our usual research practices but was in keeping with the objective of establishing meaningful patient involvement for a future definitive trial. This work was informed by concepts of critical humility, and a process of knowledge production enabled via the construction of a knowledge space.
CD4:CD8 ratio in children with perinatally acquired HIV‐1 infection
Authors: Seers T , Vassallo P , Pollock K , Thornhill JP , Fidler S , Foster C
Published: August 2018

Objectives

In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non‐AIDS‐defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART.

Methods

A cross‐sectional, retrospective analysis of routine clinical data in children with PaHIV (5–18 years old) attending a single UK centre was carried out.

Results

CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized β = −0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery.

Conclusions

We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV‐positive adults and children will enhance immunological normalization.
Difficult to diagnose small cutaneous melanoma metastases mimicking angiomas: utility of dermoscopy
Authors: Mazzella Caterina , Costa Claudia , Cappello Milena , Scalvenzi Massimiliano
Published: August 2018

Background

Metastases from melanoma can be found in any organ, while the reported incidence of skin metastases varies between 2 and 20%. Cutaneous melanoma metastases (CMM) can be heterogeneous at clinical examination, and they can simulate other benign and malignant lesions, thus generating major diagnostic troubles for the dermatologist. Dermoscopy is a useful tool that may increase the physician's diagnostic accuracy to this purpose.

Materials and methods

Herein, we describe the case of two patients having lesions that can easily be confused with other benign or malignant lesions for their clinical and dermoscopic similarities and for the variability of presentation of skin metastases. The description of the dermoscopy patterns of melanoma metastases may be useful to recognize early metastases, when clinically not suspected, facilitating an early removal and histopathological confirmation.

Results

Diagnoses of melanoma metastases and angiomas were confirmed by histological examination. Melanoma metastases show at dermoscopic examination the angioma‐like pattern. The ability to detect CMM between other lesions was good taking into consideration that, without the patient's history and with just the dermoscopy image, it could be very difficult to distinguish CMM from other benign or malignant skin lesions.

Conclusions

The present study confirms that dermoscopy is a useful tool to increase the physician's diagnostic accuracy for CMM and allow its differentiation from other cutaneous lesions, always taking into account the patient's medical record.
Distinctive lupus panniculitis of scalp with linear alopecia along Blaschko's lines: a review of the literature
Authors: Lueangarun Suparuj , Subpayasarn Urairack , Tempark Therdpong
Published: August 2018

Lupus panniculitis of the scalp (LPS) is a rare and distinctive clinical feature of lupus erythematosus panniculitis (LEP) with linear alopecia along Blaschko's lines. In this study, we investigated clinical features and treatments of LPS by literature review of articles in the English language from PubMed and SCOPUS databases up to April 2018. The following key words, “lupus panniculitis, “lupus erythematosus panniculitis”, “lupus profundus”, “head”, and “scalp”, were used. Twenty cases of LPS were identified (mean age = 26.4 [10–53] years, female: male ratio = 1:1, mean disease duration = 86.89 [8–336] weeks). The most commonly affected areas of scalp included parietal (70%), frontal (45%), temporal (40%), occipital (30%), and vertex (10%), along 70% of Blaschko's lines with morphologic lesions linear, annular, arch‐shaped, and ulcer. Besides, ANA (60%) was in particular noted. Hydroxychloroquine, oral prednisolone, intralesional corticosteroid, and methotrexate were the most common treatments, with complete response after an average period of 8.08 (2–12) weeks. Systemic lupus erythematosus (SLE) was developed in four cases (20%) during follow‐up, with high recurrence of 35%. We reported distinctive and rare cases of LPS.The continuing follow‐up was highly recommended to avoid probable recurrence and SLE development.
Decreased expression of neuregulin1 in the lesional skin of vitiligo patients
Authors: Rani Seema , Kumari Uma , Bhardwaj Supriya , Parsad Davinder , Sharma Vijay L. , Kumar Ravinder
Published: August 2018

Background

Paracrine cross‐talk exists between the fibroblasts of dermis and epidermal cells through secretions of various growth factors. Melanocytes present at the basement layer of the epidermis and respond to various factors secreted by underlying dermal fibroblasts in the dermis to regulate the function of the skin.

Objective

Therefore the study was planned to check the expression of fibroblast‐derived factor neuregulin1 (NRG1) in vitiligo skin and its effect on melanocytes.

Methods

For this study, relative gene expression at mRNA level of NRG1 in the vitiligo skin was analyzed by qRT‐PCR, and protein analysis was done by immunohistochemistry. Effect of different concentrations of NRG1 was checked on the cultured melanocytes by melanin content assay, proliferation assay, and tyrosinase (TYR) assay. The effect of NRG1 was also checked on the level of melanocyte regulatory genes (MITF, c‐KIT, TYR, DCT).

Results

Expression of NRG1 was significantly less in lesional dermis of vitiligo patients as compared to nonlesional and healthy control dermis both at mRNA as well as protein level. NRG1 treatment showed significant increase in proliferation, melanin content, TYR level, and gene expression level of melanocyte specific genes.

Conclusion

Treatment of NRG1 to the cultured melanocytes increases proliferation and pigmentation. Lower expression of NRG1 in the lesional dermis of vitiligo patients inhibits the melanocyte growth. Therefore this study hypothesized that low expression of NRG1 in lesional skin of vitiligo patients might have a possible role in the melanocyte loss and vitiligo pathogenesis.
R&D in a duopoly under incomplete information
Authors: Chatterjee Rittwik , Chattopadhyay Srobonti , Kabiraj Tarun
Published: August 2018

The availability of information about rivals may have a significant impact on a firm's decision about R&D investment. This paper investigates how the R&D incentive of a firm in a Cournot duopoly may depend on information structures. We show that asymmetric information about the rival's cost reduction may enhance the research incentive of each firm compared to the complete‐information case. However, an additional dimension of asymmetry (e.g. the information about whether the rival has invested in R&D or not) will reduce the R&D incentive unambiguously compared to the one‐dimensional asymmetry case.