bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Salesman? Hell no!’ Identity struggles of nascent design entrepreneurs
Authors: Nielsen Suna Løwe , Norlyk Birgitte , Christensen Poul Rind
Published: August 2018

The present study offers new input to the discussion of how entrepreneurship education and training programmes can be tailored to suit design professionals. To a large extent, existing entrepreneurship teaching for creative people is based on a traditional administrative management logic that often results in a clash between entrepreneurial demands and creative identities. The paper is based on the following rationale: the better we understand designers' reasoning and their struggles concerning becoming entrepreneurs, the better we are able to design entrepreneurship learning experiences that meet their needs. Since designers' career‐making tends to be highly driven by their strong sense of identity, the paper takes an identity perspective. The empirical foundation of the research is based on observation studies and phenomenological interviews conducted during an eight‐week entrepreneurship training program. Twenty‐five nascent design entrepreneurs with a professional background as designers participated in the voluntary programme. The paper offers novel and critical insights into designers' experiences of the entrepreneurial identity and reasoning as they participate in entrepreneurship training.
The telephone game, or clear as crystal? How to effectively craft responses to reviewer comments
Authors: Frishammar Johan , Thorgren Sara
Published: August 2018

This brief note focuses on how to communicate with reviewers through the response letter. Specifically, we elaborate on how to minimize the risk that reviewers underestimate the quality of the study because of poor communication in the response letter. We outline ideas for how to plan and organize a revision, and then crafting the response letter. We organize the discussion around how common writing rules, such as “Make it simple to read” and “Write for the target audience”, may apply to response letters but need adaptation to be effective. In summary, while the changes made in the actual paper are most important in any revision, this note provides an additional resource to use in order to increase the chances that the revised paper reaches its greatest potential.
Alternating magnetic field enhances cytotoxicity of Compound C
Authors: Akimoto Taisuke , Umemura Masanari , Nagasako Akane , Ohtake Makoto , Fujita Takayuki , Yokoyama Utako , Eguchi Haruki , Yamamoto Tetsuya , Ishikawa Yoshihiro
Published: August 2018

We previously reported the efficacy of anti‐cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF‐induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C‐induced cell‐cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C‐induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.
Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ1
Authors: Fujiwara Hiroaki , Tateishi Keisuke , Kato Hiroyuki , Nakatsuka Takuma , Yamamoto Keisuke , Tanaka Yasuo , Ijichi Hideaki , Takahara Naminatsu , Mizuno Suguru , Kogure Hirofumi , Matsubara Saburo , Nakai Yousuke , Koike Kazuhiko
Published: August 2018

Cholangiocarcinoma is a life‐threatening disease with a poor prognosis. Although genome analysis unraveled some genetic mutation profiles in cholangiocarcinoma, it remains unknown whether such genetic abnormalities relate to the effects of anticancer drugs. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma (ICC). Recently, the anticancer effects of BET inhibitors including JQ1 have been shown in various tumors. In the present study, we report that the antigrowth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1. RBE cells harboring IDH1 mutation was more sensitive to JQ1 than HuCCT1 or HuH28 cells with wild‐type IDH1. JQ1 induced apoptosis only in RBE cells through the upregulation of proapoptotic genes BAX and BIM. We found that the antigrowth effect was not attributed to downregulation of the MYC gene as a well‐known target of JQ1 in various cancer cells. Notably, the forced expression of mutant IDH1 successfully sensitized HuCCT1 cells to JQ1. In addition, AGI‐5198, a selective inhibitor of mutant IDH1 partially reversed the decrease in viability after JQ1 treatment and also suppressed the JQ1‐induced apoptosis in RBE cells. These data suggest that IDH1 mutation contributed to the growth inhibitory effect of JQ1 in RBE cells. Furthermore, given that the effect of mutant IDH1 was not recapitulated in glioblastoma cells, the enhancement of JQ1 sensitivity by IDH1 mutation seems to be specific for ICC cells. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC.
Cumulative and Differential Effects of Early Child Care and Middle Childhood Out‐of‐School Time on Adolescent Functioning
Authors: Vandell Deborah L. , Lee Kenneth T.H. , Whitaker Anamarie A. , Pierce Kim M.
Published: August 2018

Effects associated with early child care and out‐of‐school time (OST) during middle childhood were examined in a large sample of U.S. adolescents (N = 958). Both higher quality early child care AND more epochs of organized activities (afterschool programs and extracurricular activities) during middle childhood were linked to higher academic achievement at age 15. Differential associations were found in the behavioral domain. Higher quality early child care was associated with fewer externalizing problems, whereas more hours of early child care was linked to greater impulsivity. More epochs of organized activities was associated with greater social confidence. Relations between early child care and adolescent outcomes were not mediated or moderated by OST arrangements in middle childhood, consistent with independent, additive relations of these nonfamilial settings.
The Effect of Mother–Child Reading Time on Children's Reading Skills: Evidence From Natural Within‐Family Variation
Authors: Price Joseph , Kalil Ariel
Published: August 2018

Children's exposure to book reading is thought to be an influential input into positive cognitive development. Yet there is little empirical research identifying whether it is reading time per se, or other factors associated with families who read, such as parental education or children's reading skill, that improves children's achievement. Using data on 4,239 children ages 0–13 of the female respondents of the 1979 National Longitudinal Survey of Youth, this study applies two different methodologies to identify the causal impact of mother–child reading time on children's achievement scores by controlling for several confounding child and family characteristics. The results show that a 1 SD increase in mother–child reading time increases children's reading achievement by 0.80 SDs.
“We Don’t Belong There”: New Geographies of Homelessness, Addiction, and Social Control in Vancouver’s Inner City
Authors: Fast Danya , Cunningham David
Published: August 2018

Drawing on eight years of ethnographic research in Vancouver’s inner city, we explore how aligned processes of gentrification and poverty management are producing new geographies of homelessness, addiction, and social control for young people who use drugs and inhabit the social, spatial, and economic margins of urban space. In particular, we examine the emergence of government‐subsidized supportive housing for youth in this setting. Tracing the experiences of a small number of individuals across time, we show how this contemporary mode of urban governance is producing new forms of life and senses of place for young people in the margins, including new kinds of embodied displacement and disappearance in the city. [Youth; Addiction; Homelessness; Housing; Gentrification; Poverty Management; Lines of Flight]
Impact of the Chinese embargo against MIR162 corn on Canadian corn producers
Authors: Schmitz Troy G.
Published: August 2018

In 2009, Syngenta created two new insect‐resistant corn varieties known as Agrisure Viptera and Agrisure Duracade, which contain the MIR162 biotechnology‐enhanced genetic trait. These varieties were approved for commercial release in North America in 2010 and were planted in spring 2011. China imposed an embargo on corn imports from North America beginning on November 20, 2013, because of its zero‐tolerance policy with respect to unapproved genetic traits in imported crops. The embargo was not lifted until December 14, 2014. The embargo led to increased availability of North American corn and a reduction in the price of corn realized by Canadian producers. The relative price of a substitute method was applied to weekly data on Ontario corn prices and Saskatchewan feed barley prices. The Chinese embargo against MIR162 corn caused the corn price received by Canadian farmers to drop by an estimated 1.24% or 5.32 cents/bushel. But for the Chinese embargo against MIR162 corn, Canadian corn producers would have realized an estimated additional $29.7 million in revenue in 2013/2014.
The effect of ventilation tube insertion to the health‐related quality of life in a group of children in Southeast Anatolia
Authors: Yazici Alper , Coskun Mehmet Enes
Published: August 2018

Objective

To demonstrate the influence of ventilation tube insertion to the quality of life in a group of children in Southeast Anatolia by Otitis Media 6‐item (OM6) questionnaire.

Design

Patients who underwent ventilation tube insertion due to otitis media with effusion (OME) at Otorhinolaryngology Department of Gaziantep University between December 2016 and April 2017 were enrolled in this prospective study. All patients were evaluated with the OM‐6 survey before operation and 6 weeks after surgery.

Results

The mean age of 45 patients out of 50 accounted for 67.64 ± 42.89 months with 27 (60%) males and 18 (40%) females. The numbers of preoperative and postoperative overall OM6 scores represented a significant improvement with 4.34 and 2.16, respectively. Moreover, each domain of OM6 (physical suffering, hearing loss, speech impairment, emotional distress, activity limitations and caregiver concerns) showed statistically significant difference.

Conclusion

Ventilation tube insertion procedure provided a significant improvement in a group of children in Southeast Anatolia suffering from chronic OME in terms of Quality of Life (QOL) assessed by OM6. We believe that OM6 is a useful tool for evaluating the patients’ health‐related quality of life and for providing additional information to the caregivers’ or families’ enquiries regarding the consequences of surgical intervention.
Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients with diagnosis of pulmonary embolism for the first time in real world
Authors: Yu Yongping , Yang Li , Zhang Yuhai , Dong Liang , Xia Jingwen , Zhu Ning , Han Xinpeng , Fang Liying , Chai Yaqin , Niu Mengjie , Liu Lingli , Yang Xuemin , Qu Shuoyao , Li Shengqing
Published: August 2018

Background

The incidence and risk factors of chronic thromboembolic pulmonary hypertension (CTEPH) in patients with acute pulmonary embolism (PE) have been well reported. However, in real world, patients diagnosed with PE for the first time were usually composed of acute PE, sub‐acute PE, and chronic PE, and the cumulative incidence and risk factors of CTEPH in this cohort were still unknown.

Methods

A prospective, long‐term, follow‐up study was conducted to assess the incidence of symptomatic CTEPH in consecutive patients with PE diagnosed for the first time. Patients with unexplained persistent dyspnea during follow‐up underwent transthoracic echocardiography and, if the findings indicated pulmonary hypertension, ventilation‐perfusion lung scanning and right heart catheterization. CTEPH was confirmed if perfusion defects were present, mean pulmonary artery pressure (mPAP) ≥25 mmHg and pulmonary artery wedge pressure (PAWP) ≤15 mmHg.

Results

The cumulative incidence of CTEPH in patients with PE diagnosed for the first time was 11.2% at 3 months, 12.7% at 1 year, 13.4% at 2 years, and 14.5% at 3 years. The following factors increased the risk of CTEPH: time from symptoms to treatment of PE ≥1 month (odds ratio (OR), 14.77), intermediate (OR, 37.63) to high risk PE (OR, 39.81), segmental and sub‐segmental branch location of embolism (OR, 8.30) and PE‐related primary risk factors (OR, 5.01). 9.4% of CTEPH patients developed from acute PE, and 90.6% from sub‐acute and chronic PE.

Conclusions

In real world, CTEPH is a relatively common and serious complication in PE patients diagnosed for the first time. Early diagnosis and treatment of PE will decrease the incidence of CTEPH in these unspecified patients.
A cost analysis of early biliary strictures following orthotopic liver transplantation in the United States
Authors: Bhutiani Neal , Jones Jordan M. , Wei David , Goldstein Laura J. , Martin Robert C. G. , Jones Christopher M. , Cannon Robert M.
Published: August 2018

Introduction

To date, the financial burden of biliary strictures (BS) after orthotopic liver transplantation (OLT) has remained largely unassessed. This study sought to approximate perioperative costs associated with early BS and delineate where in the hospital these costs are incurred.

Methods

The Premier Healthcare Database was queried for patients undergoing OLT between 2010 and 2016. Patients who did and did not develop early BS were compared with respect to perioperative costs and outcome variables. Multivariable regression models were used to estimate differences between groups.

Results

Patients who developed early BS had a longer length of stay (LOS) (35.3 days vs 17.8 days, P < 0.001) and were less likely to be discharged home (odds ratio = 0.45, P = 0.003). Development of early BS was associated with an incremental cost increase of $81 881 (45.8%, P < 0.001). The greatest relative cost increases were in radiology (+163.5%) and respiratory therapy (+157.1%), while the greatest absolute increase was in room and board (+$27 589).

Conclusions

Early BS after OLT result in higher costs stemming from longer LOS and increased need for various diagnostic studies and therapies. In addition to incentivizing measures that may prevent early BS, hospitals should account for these factors when developing payment schemes for OLT with payors.
Review of the medical literature and assessment of current utilization patterns regarding the use of two common fluorescence in situ hybridization assays in the diagnosis of dermatofibrosarcoma protuberans and clear cell sarcoma
Authors: Linos Konstantinos , Kozel Jessica A. , Hurley Maria Yadira , Andea Aleodor A.
Published: August 2018

Background

Dermatofibrosarcoma protuberans (DFSP) is a tumor of intermediate malignancy, which in selected circumstances can pose difficulty in diagnosis. Clear cell sarcoma (CCS) is a very rare aggressive soft tissue sarcoma that can be difficult to distinguish histologically from melanoma.

Methods

The current literature on t(17;22) COL1A1‐PDGFB fluorescence in situ hybridization (FISH) assay in DFSP was reviewed. Also reviewed was the current literature on dual color break‐apart EWSR1 FISH assay in CCS. Finally, the current utilization patterns of these tests was assessed in attendees of the American Society of Dermatopathology annual meeting (Chicago, 2016).

Results

The literature indicates that (17;22) COL1A1‐PDGFB FISH assay has limited value for classic DFSP, where the diagnosis can be established by routine morphology and immunohistochemistry. Given the high specificity of the EWSR1 FISH assay and significant complexity in the diagnosis of CCS, this ancillary study is helpful in distinguishing CCS from melanoma.

Conclusions

In attendees, t(17;22) COL1A1‐PDGFB FISH testing for classic cases of DFSP is appropriately not being used by respondents. However, the literature sustains that it is useful in selected circumstances in which a definitive diagnosis is challenging. The majority of respondents are utilizing the EWSR1 FISH assay to distinguish CSS from melanoma as is supported by the literature.
The reciprocal relation between sleep and memory in infancy: Memory‐dependent adjustment of sleep spindles and spindle‐dependent improvement of memories
Authors: Friedrich Manuela , Mölle Matthias , Friederici Angela D. , Born Jan
Published: August 2018

Sleep spindle activity in infants supports their formation of generalized memories during sleep, indicating that specific sleep processes affect the consolidation of memories early in life. Characteristics of sleep spindles depend on the infant's developmental state and are known to be associated with trait‐like factors such as intelligence. It is, however, largely unknown which state‐like factors affect sleep spindles in infancy. By varying infants’ wake experience in a within‐subject design, here we provide evidence for a learning‐ and memory‐dependent modulation of infant spindle activity. In a lexical‐semantic learning session before a nap, 14‐ to 16‐month‐old infants were exposed to unknown words as labels for exemplars of unknown object categories. In a memory test on the next day, generalization to novel category exemplars was tested. In a nonlearning control session preceding a nap on another day, the same infants heard known words as labels for exemplars of already known categories. Central–parietal fast sleep spindles increased after the encoding of unknown object–word pairings compared to known pairings, evidencing that an infant's spindle activity varies depending on its prior knowledge for newly encoded information. Correlations suggest that enhanced spindle activity was particularly triggered, when similar unknown pairings were not generalized immediately during encoding. The spindle increase triggered by previously not generalized object–word pairings, moreover, boosted the formation of generalized memories for these pairings. Overall, the results provide first evidence for a fine‐tuned regulation of infant sleep quality according to current consolidation requirements, which improves the infant long‐term memory for new experiences.
A post‐hoc pooled analysis to evaluate the risk of hypoglycaemia with insulin glargine 300 U/mL (Gla‐300) versus 100 U/mL (Gla‐100) over wider nocturnal windows in individuals with type 2 diabetes on a basal‐only insulin regimen
Authors: Bolli Geremia B. , Wysham Carol , Fisher Miles , Chevalier Soazig , Cali Anna M. G. , Leroy Bruno , Riddle Matthew C.
Published: August 2018

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24‐hour) hypoglycaemia for insulin glargine 300 U/mL (Gla‐300) versus glargine 100 U/mL (Gla‐100). However, the predefined nocturnal window (0:00–5:59 AM) may not be the most relevant for clinical practice. This post‐hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin. Patient‐level, 6‐month data, pooled from the EDITION 2 and 3 trials and the EDITION JP 2 trial (N = 1922, basal insulin only) were analysed. Accompanying hypoglycaemia during treatment with Gla‐300 was compared to that during treatment with Gla‐100, using predefined (0:00–5:59 AM) and expanded (10:00 PM–5:59 AM, 0:00–7:59 AM, 10:00 PM to pre‐breakfast SMPG) windows. Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 6:00 AM and 8:00 AM. Windows expanded beyond 6:00 AM included more events than other windows. The percentage of participants with at least one event was lower with Gla‐300 than Gla‐100 in all windows examined. Expanding the nocturnal interval allows better assessment of the risk of hypoglycaemia associated with basal insulin. The risk of nocturnal hypoglycaemia was consistently lower with Gla‐300 versus Gla‐100 using all four windows.
Does FDI crowd out domestic investment in transition countries?
Authors: Jude Cristina
Published: August 2018

The aim of this paper is to empirically investigate the relationship between foreign direct investment (FDI) and domestic investment in a sample of 10 Central and Eastern European countries over the period 1995–2015. We find FDI to lead to a creative destruction phenomenon, with a short‐term crowding out effect on domestic investment, followed by a long‐term crowding in. Greenfield FDI develops stronger long‐run complementarities with domestic investment, while mergers and acquisitions do not show a significant effect on domestic investment. Financial development seems to mitigate crowding out pressures and even foster a crowding in for mergers and acquisitions.
“Leadership? No, Thanks!” A New Construct: Worries About Leadership
Authors: Aycan Zeynep , Shelia Salome
Published: August 2018

Leadership is considered a key career aspiration. However, in a volatile, uncertain, complex and ambiguous (VUCA) environment, is such a goal indisputably desirable? Tapping the emotion domain, we propose a new construct, worries about leadership (WAL), defined as the worries people have about the possible negative consequences of assuming a leadership role. Four studies investigated discriminant, convergent and predictive validities of WAL scale using diverse methodologies: survey, lab experiment and naturalistic field study. Findings confirmed theoretically proposed dimensions of WAL: worries about failure, work‐life imbalance, and harm. WAL was found orthogonal to Motivation to Lead (MTL; Chan & Drasgow, 2001) and correlated with neuroticism and prevention focus. Correlation of WAL scores with physiological indices of emotions was insignificant, albeit in the expected direction. WAL predicted leader emergence above and beyond MTL. These findings have significant theoretical and practical implications contributing to more nuanced understanding of leader emergence.
Place of neurosteroids in the treatment of status epilepticus
Authors: Rossetti Andrea O.
Published: August 2018

The treatment of refractory or super‐refractory status epilepticus (SE) currently relies on low‐evidence strategies, including general anesthetics to induce pharmacologic coma, ketogenic diet, immunosuppression, and other physical measures. Besides the formal uncertainty regarding efficacy, concerns have been about tolerability. In this situation, identification of alternative, higher evidence treatments is urgently needed. Allopregnanolone is an endogenous neurosteroid exerting a positive allosteric modulation on γ‐aminobutyric acid (GABA)A receptors. In animal experiments it has been demonstrated that this neurosteroid displays relevant antiseizure properties in a variety of SE models, and that the tolerance to benzodiazepines, relying on receptor internalization, does not affect its action. An experimental clinical use in patients with SE older than 2 years was initated more than 5 years ago. Being a naturally occurring compound, no relevant adverse events are expected, and until now its safety profile appears reassuring. Preliminary results of a phase I/II trial seemed promising, but a recent well‐designed randomized, placebo‐controlled trial could not find any difference in terms of efficacy; tolerability seemed nevertheless good. Patients with refractory and super‐refractory SE still deserve further well‐designed studies to improve current treatment options.
Status epilepticus in the elderly
Authors: Leppik Ilo E.
Published: August 2018

Children and the elderly (≥60 years of age) have the highest incidence ofstatus epilepticus (SE). Because of their general health, elderly individuals are much more likely than younger (<60 years of age) persons to have more severe consequences from seizures. The incidence ofSEis 15.5/100 000 in the 60‐69 age group, 21.5/100 000 in the 70‐79 age group and 25.9/100 000 in persons 80 and older. The most common cause in the elderly is acute symptomatic, with stroke and hypoxia the most frequent. The overall mortality ofSEis quite high and occurs early, often within the first few days, and is related to the cause, with mortality of more than 80% in persons with anoxia. Although the cause ofSEis an important factor in mortality, the aging body and brain may contribute to an unfavorable outcome. Treatment in the elderly is essentially the same as in younger adults with benzodiazepines (lorazepam, diazepam, clonazepam) and longer acting antiseizure drugs (phenytoin, fosphenytoin, valproate, levetiracetam, and lacosamide. At this time there are no evidence‐based studies regarding Axis 2 (etiology) and Axis 4 (age). All current interventions forSEinvolve antiseizure drugs that were developed for treatment of chronic epilepsy. Treatments should be developed that are more specific for the various etiologies and involve drugs that work on the underlying cause of theSE.
Anesthetic drugs for the treatment of status epilepticus
Authors: Hocker Sara
Published: August 2018

Worsening pharmacoresistance to antiseizure drugs is common with ongoing excitotoxic neuronal and systemic injury. Early initiation of anesthetic drugs in refractory status epilepticus (RSE) may halt these processes while allowing time for treatment targeting the cause of the seizures. Current guidelines support the use of anesthetic drugs as the third line pharmacologic therapy in generalized convulsive status epilepticus but do not clearly define the indications for these drugs in other types of status epilepticus. There is wide practice variation in choice of third line therapy for RSE, but there is overall consensus that anesthetics should be initiated earlier in generalized convulsive status epilepticus than in nonconvulsive forms. More recently, doubt has been cast on the appropriateness of anesthetic treatment of RSE following a series of studies associating their use with higher mortality and morbidity. This suggests that efforts should focus on determination of who benefits most, optimal use, and prevention of refractoriness. The risk‐benefit ratio of anesthetic use is discussed, with specific indications proposed. In addition, anesthetic dosing, supportive neurocritical care, electroencephalogram suppression target, and weaning of anesthesia are reviewed.
Epigenetic changes in status epilepticus
Authors: Henshall David C.
Published: August 2018

Epigenetics refers broadly to processes that influence medium‐ to long‐term expression of genes through changes to the readability and accessibility of the genome to transcription. The mediators include DNA methylation, posttranslational modification of histone proteins, and noncoding RNAs. The present review focuses on recent findings showing epigenetic processes influence susceptibility to and severity of status epilepticus, while status epilepticus in turn drives changes to epigenetic marks that affect the gene expression landscape underlying epileptogenesis. Experimental status epilepticus triggers select, spatiotemporal hypo‐ and hypermethylation changes throughout the genome. Experimental manipulations that alter DNA methylation after status epilepticus are associated with amelioration of cognitive and hyperexcitability phenotypes. Prolonged seizures also modify chromatin compaction via acetylation and other changes to histones and their expression. Finally, short noncoding RNAs called microRNAs target networks of genes through posttranscriptional and other mechanisms and their modulation can alter status epilepticus as well as serve as potential molecular biomarkers. Long noncoding RNAs have also been targeted to influence expression of genes affecting electrophysiological functions of neurons. In summary, epigenetic processes can modulate status epilepticus, and status epilepticus imposes changes on the epigenome, which together provide novel insight into pathomechanisms, therapy, and biomarkers for status epilepticus.
Harmonising national sanctioning administrative law: An alternative to a single capital‐markets supervisor
Authors: Pascua Mateo Fabio
Published: August 2018

Since the disclosure in 2009 of the Larosière Report, legislative acts disciplining financial markets have established a set of rules called to form the foundations of a sanctioning administrative law to be enforced by the Member States. Furthermore, the ECtHR and the ECJ, are contributing to apply here the guarantees of the Rome Convention and the Charter of Fundamental Rights. This study, in addition to giving account of such legislation and case‐law, aims to outline the broad principles of this new law, whose purpose is levelling the ‘playing field’ amongst NCAs and fostering supervisory convergence without creating new institutions. Should this ‘experiment’ be successful, and a new way of ‘cooperative federalism’ could emerge at a global level in the Union. Otherwise, further centralisation—which is neither possible nor desirable at this stage—should be expected in future years, with a sort of single supervisory mechanism in securities markets.
Weed evolution: Genetic differentiation among wild, weedy, and crop radish
Authors: Charbonneau Amanda , Tack David , Lale Allison , Goldston Josh , Caple Mackenzie , Conner Emma , Barazani Oz , Ziffer‐Berger Jotham , Dworkin Ian , Conner Jeffrey K.
Published: August 2018

Approximately 200 weed species are responsible for more than 90% of crop losses and these comprise less than one percent of all named plant species, suggesting that there are only a few evolutionary routes that lead to weediness. Agricultural weeds can evolve along three main paths: they can be escaped crops, wild species, or crop‐wild hybrids. We tested these three hypotheses in weedy radish, a weed of small grains and an emerging model for investigating the evolution of agricultural weeds, using 21 CAPS and SSR markers scored on 338 individuals from 34 populations representing all major species and sub‐species in the radish genus Raphanus. To test for adaptation of the weeds to the agricultural environment, we estimated genetic differentiation in flowering time in a series of common garden experiments with over 2,400 individuals from 43 populations (all but one of the genotyped populations plus 10 additional populations). Our findings suggest that the agricultural weed radish R. r. raphanistrum is most genetically similar to native populations of R. r. raphanistrum and is likely not a feral crop or crop hybrid. We also show that weedy radish flowers more rapidly than any other Raphanus population or cultivar, which is consistent with rapid adaptation to the frequent and severe disturbance that characterizes agricultural fields.
Population structure of a global agricultural invasive pest, Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Qin Yu‐jia , Krosch Matthew N. , Schutze Mark K. , Zhang Yue , Wang Xiao‐xue , Prabhakar Chandra S. , Susanto Agus , Hee Alvin K. W. , Ekesi Sunday , Badji Kemo , Khan Mahfuza , Wu Jia‐jiao , Wang Qiao‐ling , Yan Ge , Zhu Li‐huan , Zhao Zi‐hua , Liu Li‐jun , Clarke Anthony R. , Li Zhi‐hong
Published: August 2018

Bactrocera dorsalis, the Oriental fruit fly, is one of the world's most destructive agricultural insect pests and a major impediment to international fresh commodity trade. The genetic structuring of the species across its entire geographic range has never been undertaken, because under a former taxonomy B. dorsalis was divided into four distinct taxonomic entities, each with their own, largely non‐overlapping, distributions. Based on the extensive sampling of six a priori groups from 63 locations, genetic and geometric morphometric datasets were generated to detect macrogeographic population structure, and to determine prior and current invasion pathways of this species. Weak population structure and high genetic diversity were detected among Asian populations. Invasive populations in Africa and Hawaii are inferred to be the result of separate, single invasions from South Asia, while South Asia is also the likely source of other Asian populations. The current northward invasion of B. dorsalis into Central China is the result of multiple, repeated dispersal events, most likely related to fruit trade. Results are discussed in the context of global quarantine, trade, and management of this pest. The recent expansion of the fly into temperate China, with very few associated genetic changes, clearly demonstrates the threat posed by this pest to ecologically similar areas in Europe and North America.
Differences in the equine faecal microbiota between horses presenting to a tertiary referral hospital for colic compared with an elective surgical procedure
Authors: Stewart H. L. , Southwood L. L. , Indugu N. , Vecchiarelli B. , Engiles J. B. , Pitta D.
Published: August 2018

Background

The faecal microbiota is emerging as potentially important in intestinal disease. More research is needed to characterise the faecal microbiota from horses with colic.

Objectives

To compare the relative abundance of bacterial populations comprising the faecal microbiota in horses presenting for colic compared with an elective surgical procedure.

Study design

Prospective observational clinical study.

Methods

Admission faecal samples were collected from horses presenting for colic and elective surgical procedures. Faecal samples were extracted for genomic DNA, PCR‐ amplified, sequenced and analysed using QIIME. Species richness and Shannon diversity were estimated for each faecal sample. The extent of the relationship between bacterial communities (beta diversity) was quantified using pairwise UniFrac distances, visualised using principal coordinate analysis (PCoA) and statistically analysed using PERMANOVA. The relative abundance of bacterial populations between the two treatment groups were compared using ANCOM.

Results

Faecal bacterial communities in horses presenting for colic had fewer species (P<0.001) and lower diversity (P<0.001) compared with horses presenting for elective surgical procedures. Based on the PERMANOVA analysis, there was a significant difference in the bacterial community composition between horses admitted for colic vs. elective procedures (P = 0.001). Based on ANCOM test, at the genus level, 14 bacterial lineages differed between the two groups. The relative abundance of known commensal bacteria including Prevotella, Clostridia, Lachnospiraceae were reduced whereas Christenellaceae, Streptococcus and Sphaerochaeta were increased in horses with colic when compared with elective cases.

Main limitations

Relative low numbers and a diverse population of horses.

Conclusions

Changes in bacterial populations in the faecal microbiota of horses presenting for colic observed in this study concurs with previous studies in veterinary and human patients with gastrointestinal disease. Future studies focusing on different causes of colic, chronic or recurrent disease, and the association with histological changes within the intestine are needed.

The Summary is available in Portuguese ‐ see Supporting Information
The biological assembly of OXA‐48 reveals a dimer interface with high charge complementarity and very high affinity
Authors: Lund Bjarte Aarmo , Thomassen Ane Molden , Nesheim Birgit Helene Berg , Carlsen Trine Josefine Olsen , Isaksson Johan , Christopeit Tony , Leiros Hanna‐Kirsti S.
Published: August 2018

Many class D β‐lactamases form dimers in solution. The functional basis of the dimerization of OXA‐48‐like class D β‐lactamases is not known, but in order to understand the structural requirements for dimerization of OXA‐48, we have characterized the dimer interface. Size exclusion chromatography, small angle X‐ray scattering (SAXS), and nuclear magnetic resonance (NMR) were used to confirm the oligomeric state of OXA‐48 in solution. X‐ray crystallographic structures were used to elucidate the key interactions of dimerization. In silico residue scanning combined with site‐directed mutagenesis was used to probe hot spots of dimerization. The affinity of dimerization was quantified using microscale thermophoresis, and the overall thermostability was investigated using differential scanning calorimetry. OXA‐48 was consistently found to be a dimer in solution regardless of the method used, and the biological assembly found from the SAXS envelope is consistent with the dimer identified from the crystal structures. The buried chloride that interacts with Arg206 and Arg206′ at the dimer interface was found to enhance the thermal stability by > 4 °C and crystal structures and mutations (R189A, R189A/R206A) identified several additional important ionic interactions. The affinity for OXA‐48 R206A dimerization was in the picomolar range, thus revealing very high dimer affinity. In summary, OXA‐48 has a very stable dimer interface, facilitated by noncovalent and predominantly charged interactions, which is stronger than the dimer interfaces previously described for other class D β‐lactamases.

PDB codes

The oxacillinase‐48 (OXA‐48) R206A structure has PDB ID: 5OFT and OXA‐48 R189A has PDB ID: 6GOA.
Small fatigue crack growth behavior of titanium alloy TC4 at different stress ratios
Authors: Hu Xu‐Teng , Zhu Lei , Jiang Rong , Song Ying‐Dong , Qu Shou‐Dao
Published: August 2018

In this paper, the small fatigue crack behavior of titanium alloy TC4 at different stress ratios was investigated. Single‐edge‐notch tension specimens were fatigued axially under a nominal maximum stress of 370 MPa at room temperature. Results indicate that fatigue cracks in TC4 initiate from the interface between α and β phases or within α phase. More than 90% of the total fatigue life is consumed in the small crack initiation and growth stages. The crack growth process of TC4 can be divided into three typical stages, ie, microstructurally small crack stage, physically small crack stage, and long crack stage. Although the stress ratio has a significant effect on the total fatigue life and crack initiation life at constant σmax, its effect on crack growth rate is indistinguishable at R = −0.1, 0.1, and 0.3 when crack growth rate is plotted as a function of ∆K.
The multi‐feedstock biorefinery – Assessing the compatibility of alternative feedstocks in a 2G wheat straw biorefinery process
Authors: Zhang Heng , Lopez Pau Cabañeros , Holland Claire , Lunde Alan , Ambye‐Jensen Morten , Felby Claus , Thomsen Sune Tjalfe
Published: August 2018

For second‐generation (2G) bioethanol refineries, the feedstock supply is one of the important parameters in terms of cost and consistency. Biorefineries are in most cases designed for a specific type of feedstock. For some biorefineries, the use of multiple feedstocks is an option, but how would such feedstocks perform when used in a process designed and optimized for a specific feedstock? There is no “one‐size‐fits‐all” processing package, due to variations in composition and structure of different feedstock types, but due to the size of commercial biorefineries, only minor adjustments of the processing parameters are practically feasible. In this study, 16 alternative feedstocks were characterized and compared to the benchmark feedstock wheat straw under identical processing conditions. The alternative feedstocks studied were as follows: barley straw, rye straw, grass straw, oat straw, Norway spruce sawdust, mixed softwood sawdust, oat wrap, biogas fiber, deep litter, washed deep litter, ryegrass fiber, lucerne fiber, ryegrass chaff, mixed grain chaff, rapeseed press cake, and beer production mash. These biomasses varied in carbohydrate content and accessibility after hydrothermal pretreatment. Applying a hydrothermal pretreatment under identical conditions, the subsequent enzymatic convertibility of these biomasses ranged from 0.5% to complete conversion based on their glucan content. Water retention value was determined and correlated with enzymatic convertibility, which provided a simple method for indirect measurement of biomass recalcitrance. Ethanol potentials were estimated based on carbohydrate release from enzymatic hydrolysis, and yeast toxicity test was performed on liquid fractions from hydrothermal pretreatment. Furthermore, a number of key processing indicators, including market price, logistics and availability, were taken into consideration based on a proposed full‐scale 2G ethanol plant in Denmark. The overall results show that while some feedstocks had inferior performance compared to wheat straw, identical or even superior performance was observed from barley, oat, and ryegrass feedstocks.
Automated Time Series Measurement of Microbial Concentrations in Groundwater‐Derived Water Supplies
Authors: Owens David W. , Hunt Randall J. , Firnstahl Aaron D. , Muldoon Maureen A. , Borchardt Mark A.
Published: August 2018

Fecal contamination by human and animal pathogens, including viruses, bacteria, and protozoa, is a potential human health hazard, especially with regards to drinking water. Pathogen occurrence in groundwater varies considerably in space and time, which can be difficult to characterize as sampling typically requires hundreds of liters of water to be passed through a filter. Here we describe the design and deployment of an automated sampler suited for hydrogeologically and chemically dynamic groundwater systems. Our design focused on a compact form to facilitate transport and quick deployment to municipal and domestic water supplies. We deployed a sampler to characterize water quality from a household well tapping a shallow fractured dolomite aquifer in northeast Wisconsin. The sampler was deployed from January to April 2017, and monitored temperature, nitrate, chloride, specific conductance, and fluorescent dissolved organic matter on a minute time step; water was directed to sequential microbial filters during three recharge periods that ranged from 5 to 20 days. Results from the automated sampler demonstrate the dynamic nature of the household water quality, especially with regard to microbial targets, which were shown to vary 1 to 2 orders of magnitude during a single sampling event. We believe assessments of pathogen occurrence and concentration, and related assessments of drinking well vulnerability, would be improved by the time‐integrated characterization provided by this sampler.
CYP7A1 expression in hepatocytes is retained with upregulated fibroblast growth factor 19 in pediatric biliary atresia
Authors: Hasegawa Yasuhiro , Kawai Masanobu , Bessho Kazuhiko , Yasuda Kie , Ueno Takehisa , Satomura Yoshinori , Konishi Akiko , Kimura Takeshi , Ikeda Kayo , Tachibana Makiko , Miyoshi Yoko , Michigami Toshimi , Kondou Hiroki , Ozono Keiichi
Published: August 2018

Aim

Bile acid biosynthesis is strictly regulated under physiological conditions. The expression of fibroblast growth factor (FGF) 19 is induced when bile acids bind to the farnesoid X receptor in the intestinal epithelium. Fibroblast growth factor 19 is then transported by the portal flow, causing transcriptional inhibition of cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1), a key enzyme in bile acid biosynthesis, through the extracellular signal‐regulated kinase (ERK) pathway. However, the regulatory mechanisms of these signaling pathways in hepatocytes under chronic cholestasis remain unclear. We investigated the regulation of these signaling pathways in patients with biliary atresia (BA).

Methods

We analyzed the regulation of molecules in these signaling pathways using liver and serum samples from eight BA children and four non‐cholestatic disease controls.

Results

CYP7A1 mRNA expression was not inhibited in BA microdissected hepatocyte‐enriched tissue (HET) despite high serum bile acid concentrations. The FGF19 protein was synthesized in BA HET, and its serum concentration was elevated. Fibroblast growth factor receptor 4 was phosphorylated in BA livers. However, ERK phosphorylation was significantly reduced. We examined SPRY2 expression to determine how the ERK pathway was inactivated downstream of the FGF receptor; the expression was significantly increased in BA HET.

Conclusions

This is the first study to measure the CYP7A1 mRNA levels in human BA HET. Fibroblast growth factor 19 was increased in BA hepatocytes. By focusing on its regulation in hepatocytes, we showed that the FGF19 pathway did not suppress bile acid synthesis, probably due to an altered mechanism involving upregulated SPRY2 in BA patients.
The Assent of Faith and the Unity of the Form in Biblical Exegesis: Balthasar’s Response to Rahner
Authors: Clarke Kevin M.
Published: August 2018

Karl Rahner and Hans Urs von Balthasar pushed back in various ways against the tide of historical criticism in the twentieth century. On the one hand Rahner wished to distance theology from biblical revelation in his turn towards the subject. In so doing, he sought to preserve theology from the rising tide of skepticism resulting from contemporary exegesis. His philosophical system left little room for historical revelation because of a fixation on individual revelation. Balthasar, on the other hand, questioned whether the Rahnerian system strips Christianity of the need to bear witness to the world, and relativizes Christ’s Incarnation. Balthasar saw the indestructible unity of the form (gestalt) presented to humanity in the revelation of Old and New Testaments as an antidote to the fragmentation within biblical studies. Because of gestalt, Scripture is more than a mere sum of its parts. For Balthasar, the faith of the exegete is an irreplaceable requisite for accurate hermeneutics. Dispensing with the revelatory character of the Scriptures would also be unscientific; it is an unsuitable approach to a text that calls one to bear witness. Balthasar thus correctly called for a theological hermeneutic whereby the faithful exegete recognizes the unity of the scriptural account.
2BIC: taking your adventuring gear to organise pop‐up health information literacy sessions
Authors: Vandendriessche Thomas , Michels Marleen , Stoop Linda , Vissenaekens Natasja , Discart Inge
Published: August 2018

Academic libraries play an important role in the provision of health information literacy (IL) skills and there are many approaches to how these can be delivered. In this paper, guest writers Inge Discart and colleagues fromKULeuven Libraries 2Bergen Information Centre (2BIC) in Belgium discuss a pop‐up information literacy skills project. In particular, the article presents the findings from an initial information skills needs assessment conducted at the University, followed by how the concept of the pop‐up sessions was developed and promoted throughout the organisation. The paper identifies the variety of sessions offered and the format in which they were delivered, with final results on how these were received and which sessions were the most popular. This article provides insight into an alternative approach to health information skills delivery and the outcomes from it.

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Maintaining your momentum
Authors: Grant Maria J.
Published: August 2018

After the excitement of this summer's Health Libraries Group conference, it is important to maintain that sense of momentum and enthusiasm that being with like‐minded library and information workers can bring. #HLG2018 certainly presented plenty of opportunities for collaboration and the enthusiasm to put ideas into action. The launch of CILIP's Health Hub, bringing together content and resources co‐produced with CILIP members, together with additional categories specifically designed for those working in health to extend CILIP's. Professional Knowledge and Skills Base (PKSB) to that of PKSB for Health means there is every reason and resource available to help maintain your momentum and enthusiasm.