bluuebunny/crossref_metadata_2025 huggingface dataset:
The USTC complex co-opts an ancient machinery to drive piRNA transcription inC. elegans
Authors: Weng Chenchun , Kosalka Asia , Berkyurek Ahmet C. , Stempor Przemyslaw , Feng Xuezhu , Mao Hui , Zeng Chenming , Li Wen-Jun , Yan Yong-Hong , Dong Meng-Qiu , Zuliani Cecilia , Barabas Orsolya , Ahringer Julie , Guang Shouhong , Miska Eric A.
Published: July 2018

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and non-self nucleic acids, maintain genome integrity, and are essential for fertility in a variety of organisms. InC. elegansmost piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC complex contains PRDE-1, TOFU-4, TOFU-5 and SNPC-4. The USTC complex form a unique piRNA foci in germline nuclei and coat the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and to form the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other non-coding RNA genes. These results reveal USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defence against transposons.
Identifying the cognitive processes underpinning hippocampal-dependent tasks
Authors: Clark Ian A. , Hotchin Victoria , Monk Anna , Pizzamiglio Gloria , Liefgreen Alice , Maguire Eleanor A.
Published: July 2018

Autobiographical memory, future thinking and spatial navigation are critical cognitive functions that are thought to be related, and are known to depend upon a brain structure called the hippocampus. Surprisingly, direct evidence for their interrelatedness is lacking, as is an understanding of why they might be related. There is debate about whether they are linked by an underlying memory-related process or, as has more recently been suggested, because they each require the endogenous construction of scene imagery. Here, using a large sample of participants and multiple cognitive tests with a wide spread of individual differences in performance, we found that these functions are indeed related. Mediation analyses further showed that scene construction, and not memory, mediated (explained) the relationships between the functions. These findings offer a fresh perspective on autobiographical memory, future thinking, navigation, and also on the hippocampus, where scene imagery appears to play an influential role.
TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity
Authors: Aiken Jayne , Moore Jeffrey K. , Bates Emily A.
Published: July 2018

‘Tubulinopathies’ are severe human brain malformations associated with mutations in tubulin genes. Despite the identification of many tubulin mutations in patients, we do not understand how these mutations impact the microtubule cytoskeleton, how the changes to microtubule function lead to brain malformations, or how different tubulin isotypes regulate microtubules to support normal neurodevelopment. TUBA1A α-tubulin is the most commonly affected tubulin isotype in tubulinopathy patients. Heterozygous mutations in TUBA1A have been identified in patients with diverse cortical malformations including microlissencephaly, lissencephaly, pachygyria, and polymicrogyria. Here we focus on mutations affecting the conserved arginine at position 402 (R402), which account for 30% of all reported TUBA1A mutations in patients. We demonstrate that exogenous expression of TUBA1A-R402C and TUBA1A-R402H patient alleles is sufficient to dominantly disrupt cortical neuron migration in the developing mouse brain, recapitulating the human lissencephaly phenotype. Intriguingly, ectopic expression of TUBA1A-R402C/H alleles does not alter morphology, axonal trafficking, or microtubule polymerization rates in cultured neurons, but does lead to subtle changes in axonal microtubule orientation. Further, we find that budding yeast α-tubulin with analogous R402C and R402H mutations assembles into microtubules but disrupts the activity of the microtubule motor dynein. The level of dynein impairment scales with abundance of R402 mutant α-tubulin in the cell. Together, our results support a model in which tubulinopathy mutations at R402 poison the microtubule network in young neurons by creating defective binding sites for dynein at the microtubule surface.
Bonding capability of Nigerian contracting firms
Authors: Oke Ayodeji Emmanuel
Published: July 2018

Purpose

The ability of construction contractors to engage in construction bond agreement with guarantors depends on capital, experience, capacity and continuity. Using these criteria, the purpose of this paper is to provide insights into the bonding capacity of Nigerian contractors.

Design/methodology/approach

Factors required for bonding were examined based on a set of questions addressed to managers of contracting firms and personnel involved in issuing bonds and guarantees in commercial banks and insurance companies. The scorecard approach was employed to determine the bonding capability of the contractors.

Findings

Contractors’ financial strength and past performance on previous projects are the two important factors considered by guarantors in granting bond to contractors. However, the condition surrounding the bond, the legal capacity of the guarantor to issue bond and the identity of the guarantor are mostly considered by contractors in approaching a potential guarantor. Using the scorecard approach, about one-third of contractors have the necessary requirements to engage in construction bond agreement with guarantors. This ability of contractors is affected by years of experience of the firm but not by their location nor years of experience of their manager.

Practical implications

It is necessary for contracting firms to increase their capital base through merging, borrowing, etc., and also engage experienced professionals and workers in the execution of construction projects, as this will eventually improve their bonding ability.

Social implications

The study is limited to construction contractors registered with Ondo and Lagos State Governments and guarantors that are banks and insurance companies in Nigeria.

Originality/value

The paper specified various areas of concerns for Nigerian contracting firms in their bid to enhance their bonding ability. This will help them in overcoming various challenges and bottlenecks that may arise in securing bonds and guarantees from guarantors.
An investigation into public and private clients’ attitudes, commitment and impact on construction health and safety in Nigeria
Authors: Umeokafor Nnedinma
Published: July 2018

Purpose

This purpose of this paper is to report the findings of a study that assessed the attitudes, commitment and impact of public and private sector clients’ involvement in construction health and safety (H&S) in Nigeria.

Design/methodology/approach

Structured questionnaires were designed based on literature review and a pilot study, and administered to public and private clients in Nigeria’s construction industry. Descriptive and inferential statistics were employed to analyse the data.

Findings

The result shows that while clients’ attitudes towards H&S are not encouraging, public clients commitment and attitudes are better than that of private clients. This is emphasised by the significant difference between the categories of clients and: accident investigation; clients auditing contractors H&S records at the preconstruction stage. The common client H&S practice includes conducting site visits and inspections and attending H&S meetings, while engaging in H&S awareness and H&S audit during construction are not common. However, when clients are involved in H&S, it has resulted in a reduction in accidents, compensation claims, rework and improved the relationship between clients and contractors.

Practical implications

The findings form a basis for improving client involvement in H&S (factoring in the differences in clients) which policymakers, the construction industry and academics will find beneficial.

Originality/value

The study contributes to understanding the attitudes and commitment of public and private clients in H&S, evidencing the implications of the differences in their needs, characteristics and behaviours. While the study is the first to investigate the area in Nigeria, it also extends the knowledge of the discourse comparatively in broader terms.
The evolution of stakeholder management practices in Australian mega construction projects
Authors: Yang Rebecca Jing , Jayasuriya Sajani , Gunarathna Chathuri , Arashpour Mehrdad , Xue Xiaolong , Zhang Guomin
Published: July 2018

Purpose

The complicated nature of megaprojects requires appropriate analysis of multiple stakeholders to achieve project objectives and to accommodate stakeholder interests. During the last two decades, many stakeholder theories and empirical studies have sprouted. Although previous studies have contributed to the development of stakeholder theory, it seems that these theoretical advances have not been fully adopted and acknowledged in practices, especially in megaprojects. The purpose of this paper is to explore the evolution of stakeholder analysis and engagement practices adopted in the Australian megaprojects over the last two decades.

Design/methodology/approach

Four mega construction projects are described and analysed in this study. Secondary data were first assembled in order to get general knowledge of each case. Interviews were conducted with the project directors. Project documents were collected from the project teams and reviewed. Wherever the project information was unclear, e-mails were sent to the directors and the team members to confirm the details.

Findings

Project teams have started to apply snowball rolling and stakeholder attribute assessment methods to analyse stakeholders. However, there is still a way to adopt the “network” analysis perspective because the project teams are reluctant to use complicated tools which need specialists’ assistance. The stakeholder engagement practices have evolved to an extent where the project teams monitor the dynamics of stakeholders’ requirements. Projects teams have identified the importance of continuity to manage stakeholders in these massive projects. However, a structured method selection mechanism for stakeholder engagement has not been developed.

Originality/value

This study will help academics to understand the adoption progress and status of stakeholder management methods.
A structural equation modelling approach for adoption of e-book amongst mathematics and statistics (MAS) students at higher education institutions in Libya
Authors: Smeda Asma , Shiratuddin Mohd Fairuz , Wong Kok Wai
Published: July 2018

Purpose

The purpose of this paper is to investigate the factors that may impact on the acceptance of the e-book amongst mathematics and statistics (MAS) students at higher education institutions in Libya.

Design/methodology/approach

A theoretical model has been developed based on the technology acceptance model (TAM). The factors divided into three groups: intrinsic variables represent the first group of factors that are related to the user or the potential users itself, such as Self-Efficacy and Resistance to Change. Second, extrinsic variables include all the factors that reflect the characteristics of the e-book and the infrastructure for universities, which are Mobility (M), Facilities (F) and Library Service Quality (LS). TAM constructs from Perceived Ease Of Use (PEOU), Perceived Usefulness (PU), Attitude (AU) and Behaviour Intention (BI) represent the last group. Data relating to the constructs were collected through a self-administered survey in 2014. The developed model was measured and tested by structural equation modelling using AMOS (22.0).

Findings

The result confirmed that the structural model fits the data well. According to the results, TAM constructs have a significant impact on the acceptance of e-book among MAS students at universities in Libya. In addition, the intrinsic variables play the important role to predict students’ BI. Although the extrinsic variables were less important, Facilities was the strong factor in this group.

Originality/value

The adoption of e-book amongst higher education students in Libya is still quite low. Hence, identifying the factors that may contribute to e-book adoption is crucial. The contribution of this paper is to determine the factors that effect on the acceptance of e-book amongst MAS students at higher education institutions in Libya.
A compound method for random noise attenuation
Authors: Gemechu Diriba , Ma Jianwei , Yong Xueshan
Published: July 2018

Random noise attenuation, preserving the events and weak features by improving signal‐to‐noise ratio and resolution of seismic data are the most important issues in geophysics. To achieve this objective, we proposed a novel seismic random noise attenuation method by building a compound algorithm. The proposed method combines sparsity prior regularization based on shearlet transform and anisotropic variational regularization. The anisotropic variational regularization which is based on the linear combination of weighted anisotropic total variation and anisotropic second‐order total variation attenuates noises while preserving the events of seismic data and it effectively avoids the fine‐scale artefacts due to shearlets from the restored seismic data. The proposed method is formulated as a convex optimization problem and the split Bregman iteration is applied to solve the optimization problem. To verify the effectiveness of the proposed method, we test it on several synthetic seismic datasets and real datasets. Compared with three methods (the linear combination of weighted anisotropic total variation and anisotropic second‐order total variation, shearlets and shearlet‐based weighted anisotropic total variation), the numerical experiments indicate that the proposed method attenuates random noises while alleviating artefact and preserving events and features of seismic data. The obtained result also confirms that the proposed method improves the signal‐to‐noise ratio.
Fencing solves human‐wildlife conflict locally but shifts problems elsewhere: A case study using functional connectivity modelling of the African elephant
Authors: Osipova Liudmila , Okello Moses M. , Njumbi Steven J. , Ngene Shadrack , Western David , Hayward Matt W. , Balkenhol Niko
Published: July 2018

Fencing is one of the most common methods of mitigating human‐wildlife conflicts. At the same time, fencing is considered one of the most pressing threats emerging in conservation globally. Although fences act as barriers and can cause population isolation and fragmentation over time, it is difficult to quantitatively predict the consequences fences have for wildlife.

Here, we model how fencing designed to mitigate human‐elephant conflict (HEC) on the Borderlands between Kenya and Tanzania will affect functional connectivity and movement corridors for African elephants. Specifically, we (a) model functional landscape connectivity integrating natural and anthropogenic factors; (b) predict seasonal movement corridors used by elephants in non‐protected areas; and (c) evaluate whether fencing in one area can potentially intensify human‐wildlife conflicts elsewhere.

We used GPS movement and remote sensing data to develop monthly step‐selection functions to model functional connectivity. For future scenarios, we used an ongoing fencing project designed for HEC mitigation within the study area. We modelled movement corridors using least‐cost path and circuit theory methods, evaluated their predictive power and quantified connectivity changes resulting from the planned fencing.

Our results suggest that fencing will not cause landscape fragmentation and will not change functional landscape connectivity dramatically. However, fencing will lead to a loss of connectivity locally and will increase the potential for HEC in new areas. We estimate that wetlands, important for movement corridors, will be more intensively used by the elephants, which may also cause problems of overgrazing. Seasonal analysis highlights an increasing usage of non‐protected lands in the dry season and equal importance of the pinch point wetlands for preserving overall function connectivity.

Synthesis and applications. Fencing is a solution to small‐scale human‐elephant conflict problems but will not solve the issue at a broader scale. Moreover, our results highlight that it may intensify the conflicts and overuse of habitat patches in other areas, thereby negating conservation benefits. If fencing is employed on a broader scale, then it is imperative that corridors are integrated within protected area networks to ensure local connectivity of affected species.
Resveratrol inhibits VEGF‐induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation
Authors: Wu Hongyan , He Liwei , Shi JingJing , Hou Xianbang , Zhang Hongjiang , Zhang Xiaoping , An Qing , Fan Fangtian
Published: July 2018

Endothelial cells (ECs) mainly depend on aerobic glycolysis to generate angiogenesis. Deregulation of glycolysis is often observed in human endothelial cells during angiogenesis. In the present study, we first report that resveratrol (RST), which has been intensively studied in glucose metabolism of various cancer cells, has a profound inhibitory effect on tube formation and migration via suppression of glycolysis in human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor (VEGF). Moreover, we further reveal that RST reduced the mRNA and protein level of glucose transporter‐1(GLUT1), hexokinase II (HK2), phosphofructokinase‐1(PFK1) and pyruvate kinase M2 (PKM2) through modulation of ERK‐mediated PKM2 nuclear translocation. Our results provide a novel mechanism to account for the inhibition of RST on VEGF‐mediated angiogenesis and suggest that targeting aerobic glycolysis or nuclear PKM2 may be a new approach for pathological angiogenesis prevention or treatment.
The mutual interplay between calcification and coccolithovirus infection
Authors: Johns Christopher T. , Grubb Austin R. , Nissimov Jozef I. , Natale Frank , Knapp Viki , Mui Alwin , Fredricks Helen F. , Van Mooy Benjamin A. S. , Bidle Kay D.
Published: July 2018

Two prominent characteristics of marine coccolithophores are their secretion of coccoliths and their susceptibility to infection by coccolithoviruses (EhVs), both of which display variation among cells in culture and in natural populations. We examined the impact of calcification on infection by challenging a variety of Emiliania huxleyi strains at different calcification states with EhVs of different virulence. Reduced cellular calcification was associated with increased infection and EhV production, even though calcified cells and associated coccoliths had significantly higher adsorption coefficients than non‐calcified (naked) cells. Sialic acid glycosphingolipids, molecules thought to mediate EhV infection, were generally more abundant in calcified cells and enriched in purified, sorted coccoliths, suggesting a biochemical link between calcification and adsorption rates. In turn, viable EhVs impacted cellular calcification absent of lysis by inducing dramatic shifts in optical side scatter signals and a massive release of detached coccoliths in a subpopulation of cells, which could be triggered by resuspension of healthy, calcified host cells in an EhV‐free, ‘induced media’. Our findings show that calcification is a key component of the E. huxleyi‐EhV arms race and an aspect that is critical both to the modelling of these host–virus interactions in the ocean and interpreting their impact on the global carbon cycle.
A frameshift mutation in the rRNA large subunit methyltransferase gene rlmAII determines the susceptibility of a honey bee pathogen Melissococcus plutonius to mirosamicin
Authors: Takamatsu Daisuke , Yoshida Emi , Watando Eri , Ueno Yuichi , Kusumoto Masahiro , Okura Masatoshi , Osaki Makoto , Katsuda Ken
Published: July 2018

American foulbrood (AFB) and European foulbrood (EFB) caused by Paenibacillus larvae and Melissococcus plutonius, respectively, are major bacterial infections of honey bees. Although macrolides (mirosamicin [MRM] and tylosin) have been used to prevent AFB in Japan, macrolide‐resistant P. larvae have yet to be found. In this study, we revealed that both MRM‐resistant and ‐susceptible strains exist in Japanese M. plutonius and that a methyltransferase gene (rlmA
II) was disrupted exclusively in MRM‐susceptible strains due to a single‐nucleotide insertion. The M. plutonius RlmAII modified G748 of 23S rRNA, and the deletion of rlmA
II resulted in increased susceptibility to MRM and the loss of modification at G748, suggesting that methylation at G748 by RlmAII confers MRM resistance in M. plutonius. The single‐nucleotide mutation in MRM‐susceptible strains was easily repaired by spontaneous deletion of the inserted nucleotide; however, intact rlmA
II was only found in Japanese M. plutonius and not in a Paraguayan strain tested or any of the whole‐genome‐sequenced European strains. MRM has been used in apiculture only in Japan. Although M. plutonius is not the target of this drug, the use of MRM as a prophylactic drug for AFB may have influenced the antibiotic susceptibility of the causative agent of EFB.
Linear Parks and the Political Ecologies of Permeability: Environmental displacement in São Paulo, Brazil
Authors: Millington Nate
Published: July 2018

This article considers the politics of resettlement within ongoing efforts to construct the Tietê River Valley Park (Parque Várzeas do Tietê), a linear park that upon completion will be the largest linear park in the world. Located in the eastern periphery of São Paulo, Brazil, the proposed project uses riverbank naturalization to dampen floodpeaks and bring green space to underserved populations. Due to the presence of low‐income neighborhoods on the river's edge, however, the project calls for the removal of roughly 40,000 people. Drawing from urban political ecology and contemporary concerns about environmentally induced displacement, I consider the conflicts over resettlement that mark the project. I analyze the project itself and situate it within a regional context defined by autoconstruction, regularized flooding, and insecure tenure. I argue that despite claims that the project will yield less risky lives for displaced residents, the form through which the project is being developed actually puts displaced residents in heightened situations of risk. I consider how communities have organized to resist displacement, and call for an approach to governance in peripheral landscapes that takes seriously the histories of collective infrastructural provisioning and autoconstructed housing that have marked them for decades.
Medical Care Costs for Recurrent versus De Novo Stage IV Cancer by Age at Diagnosis
Authors: Ritzwoller Debra P. , Fishman Paul A. , Banegas Matthew P. , Carroll Nikki M. , O'Keeffe‐Rosetti Maureen , Cronin Angel M. , Uno Hajime , Hornbrook Mark C. , Hassett Michael J.
Published: July 2018

Objective

To address the knowledge gap regarding medical care costs for advanced cancer patients, we compared costs for recurrent versus de novo stage IV breast, colorectal, and lung cancer patients.

Data Sources/Study Setting

Virtual Data Warehouse (VDW) information from three Kaiser Permanente regions: Colorado, Northwest, and Washington.

Study Design

We identified patients aged ≥21 with de novo or recurrent breast (nde novo = 352; nrecurrent = 765), colorectal (nde novo = 1,072; nrecurrent = 542), and lung (nde novo = 4,041; nrecurrent = 340) cancers diagnosed 2000–2012. We estimated average total monthly and annual costs in the 12 months preceding, month of, and 12 months following the index de novo/recurrence date, stratified by age at diagnosis (<65, ≥65). Generalized linear repeated‐measures models controlled for demographics and comorbidity.

Principal Findings

In the pre‐index period, monthly costs were higher for recurrent than for de novo breast (<65: +$2,431; ≥65: +$1,360), colorectal (<65: +$3,219; ≥65: +$2,247), and lung cancer (<65: +$3,086; ≥65: +$2,260) patients. Conversely, during the index and post‐index periods, costs were higher for de novo patients. Average total annual pre‐index costs were five‐ to ninefold higher for recurrent versus de novo patients <65.

Conclusions

Cost differences by type of advanced cancer and by age suggest heterogeneous patterns of care that merit further investigation.
Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue
Authors: Villarroya Joan , Gallego‐Escuredo José M. , Delgado‐Anglés Alejando , Cairó Montserrat , Moure Ricardo , Gracia Mateo Ma , Domingo Joan C. , Domingo Pere , Giralt Marta , Villarroya Francesc
Published: July 2018

Fibroblast growth factor 21 (FGF21) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating FGF21 levels are increased with aging in rodents and humans. Moreover, despite the metabolic health‐promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21. Here, we investigated serum FGF21 levels and expression of genes encoding components of the FGF21‐response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum FGF21 levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA‐IR, indices of mildly deteriorated glucose homeostasis. Levels of β‐Klotho, the coreceptor required for cellular responsiveness to FGF21, were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor‐1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to FGF21 “ex vivo”. Thus, in contrast to what is observed in obesity and diabetes, high levels of FGF21 in healthy aging are not associated with repressed FGF21‐responsiveness machinery in adipose tissue. The lack of evidence for impaired FGF21 responsiveness in adipose tissue establishes a distinction between alterations in the FGF21 endocrine system in aging and chronic metabolic pathologies.
Computational Modeling of Oxygen Transfer in Artificial Lungs
Authors: Kaesler Andreas , Rosen Marius , Schmitz‐Rode Thomas , Steinseifer Ulrich , Arens Jutta
Published: July 2018

Under physiological conditions, up to 97% of the oxygen in blood that is transported from lungs to tissue is bound to hemoglobin. To predict oxygen transfer in artificial lungs on a membrane fiber level with computational fluid dynamics (CFD), previous investigators have incorporated the hemoglobin‐oxygen interaction into an effective diffusivity coefficient to modify the convection‐diffusion equation. Based on our own simulations and experiments, these approaches tend to significantly overestimate the oxygen transfer. The present study introduces a novel approach to model the oxygen transfer in blood on a fiber level with CFD. Plasma and red blood cells were implemented as two phases and the reaction of hemoglobin and oxygen to oxyhemoglobin was included in the convection‐diffusion equation in form of a source term. The model was implemented with the commercial software Ansys CFX 18.1. CFD simulations were compared with in vitro experiments on three micro oxygenators with a staggered fiber configuration under multiple blood flow conditions. To calibrate the model, a reaction rate R0 was introduced and experimental data was fitted to a blood flow of 50 mL/h. Our model approximated the oxygen transfer rates with a difference, relative to in vitro results, of −23.7 and +6.3% for blood flows of 20 and 90 mL/h, respectively. The effective diffusivity model, used by previous authors, was implemented for comparison and approximated oxygen transfer rates with a difference, relative to in vitro data, of +13.7, +68.8, and +121.0% for blood flows of 20, 50, and 90 mL/h, respectively. A well‐established numerical mass transfer correlation approximated the gas transfer with a difference, referenced on the average in vitro data, of 31.8, 13.1, and 5.0% for blood flows of 20, 50, and 90 mL/h, respectively. Even though results are promising, a thorough validation of the model will require extensive CFD and in vitro studies of multiple fiber arrangements, fiber diameters, and therefore fiber bundle porosities in the future. This article should be understood as a first feasibility study to evaluate the potential of the novel oxygen transfer model.
Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department
Authors: Cozzi Giorgio , Zanchi Chiara , Chiaretti Antonio , Tipo Vincenzo , Cernich Marta , D'Anna Carolina , Fantacci Claudia , Conversano Ester , Zanon Davide , Ronfani Luca , Barbi Egidio
Published: July 2018

Aim

Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually.

Methods

We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self‐reported pain was at least six on a scale from 0–10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours.

Results

The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9–14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0–4.3) and tramadol 3.0 (IQR 1.0–5.0) vs paracetamol 3.0 (IQR 0.8–5.0). The median pain reductions were all 5.0 points.

Conclusion

Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.
Fetal vascular malperfusion, an update
Authors: Redline Raymond W. , Ravishankar Sanjita
Published: July 2018

Fetal vascular malperfusion is the most recent term applied to a group of placental lesions indicating reduced or absent perfusion of the villous parenchyma by the fetus. The most common etiology of malperfusion is umbilical cord obstruction leading to stasis, ischemia, and in some cases thrombosis. Other contributing factors may include maternal diabetes, fetal cardiac insufficiency or hyperviscosity, and inherited or acquired thrombophilias. Severe or high grade fetal vascular malperfusion is an important risk factor for adverse pregnancy outcomes including fetal growth restriction, fetal CNS injury, and stillbirth. Overall recurrence risk for subsequent pregnancies is low.
Editorial: aminosalicylates in Crohn's disease—prevalence, risks, costs and time to re‐assess?
Authors: Mansfield J. , MacDougall L.
Published: July 2018

Linked Content

This article is linked to Ma et al and Jairath et al papers. To view these articles visit https://doi.org/10.1111/apt.14821 and and https://doi.org/10.1111/apt.14908.
Editorial: covert hepatic encephalopathy—silent but serious. Authors’ reply
Authors: Labenz C. , Wörns M.‐A.
Published: July 2018

Linked Content

This article linked to Labenz et al and Neuberger papers. To view these articles visit https://doi.org/10.1111/apt.14824 and https://doi.org/10.1111/apt.14857.
Editorial: diabetes in HIV‐infected patients—do not blame the usual suspect! Authors’ reply
Authors: Provoost A. , Dramé M. , Bani‐Sadr F.
Published: July 2018

Linked Content

This article is linked to Provoost et al and Höner zu Siederdissen and Mederacke papers. To view these articles visit https://doi.org/10.1111/apt.14812 and https://doi.org/10.1111/apt.14863.
Editorial: deciding when to intervene in primary sclerosing cholangitis
Authors: Stratton L. , Williams M. J.
Published: July 2018

Linked Content

This article is linked to Zenouzi et al paper. To view this article visit https://doi.org/10.1111/apt.14797.
Editorial: Tong‐Xie‐Yao‐Fang (TXYF) for irritable bowel syndrome with diarrhoea (IBS‐D)—ancient medicine meets modern study
Authors: Vitta S. , Sayuk G. S.
Published: July 2018

Linked Content

This article is linked to Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14817 and https://doi.org/10.1111/apt.14906.
Addressing Food Insecurity in College: Mapping a Shared Conceptual Framework for Campus Pantries in Michigan
Authors: Reppond Harmony A. , Thomas‐Brown Karen , Sampson Natalie R. , Price Carmel E.
Published: July 2018

The first known university food pantry started at Michigan State University in 1993. Since then, campus food pantries are more widespread, although little is known about them. The current study examined how college pantries best serve students and foster their success. Twenty‐eight food pantry directors and staff from across sixteen Michigan college campuses engaged in concept mapping, a technique used to examine the interrelationships among concepts understood by stakeholders. Analyses identified six concepts, examined importance of each concept as assigned by participants, and evaluated variation among institutions. Implications for findings and future research directions are discussed.
Personalized prediction model for seizure‐free epilepsy with levetiracetam therapy: a retrospective data analysis using support vector machine
Authors: Zhang Jia‐hui , Han Xiong , Zhao Hong‐wei , Zhao Di , Wang Na , Zhao Ting , He Gui‐nv , Zhu Xue‐rui , Zhang Ying , Han Jiu‐yan , Huang Dian‐ling
Published: July 2018

Aims

To predict the probability of a seizure‐free (SF) state in patients with epilepsy (PWEs) after treatment with levetiracetam and to identify the clinical and electroencephalographic (EEG) factors that affect outcomes.

Methods

Retrospective analysis of PWEs treated with levetiracetam for 3 years identified 22 patients who were SF and 24 who were not. Before starting levetiracetam, 11 clinical factors and four EEG features (sample entropy of α, β, θ, δ) were identified. Overall, 80% of each the two groups were chosen to establish a support vector machine (SVM) model with 5‐fold cross‐validation, hold‐out validation and jack‐knife validation. The other 20% were used to predict the efficacy of levetiracetam. The mean impact value (MIV) algorithm was used to rank the relativity between factors and outcomes.

Results

Compared with SF patients, not SF patients displayed a specific decrease in EEG sample entropy in α band from the F4 channel, β band from Fp2 and F8 channels, θ band from C3 channel (P < 0.05). The SVM model based on the clinical and EEG features yielded 72.2% accuracy of 5‐fold cross‐validation, 75.0% accuracy of jack‐knife validation, 67.7% accuracy of hold‐out validation in the training set and had a high prediction accuracy of 90% in test set (sensitivity was 100%, area under the receiver operating characteristic curve was 0.96). The feature of β band from Fp2 weighs heavily in the prediction model according to the mean impact value algorithm.

Conclusions

The efficacy of levetiracetam on newly diagnosed PWEs could be predicted using an SVM model, which could guide antiepileptic drug selection.
A comprehensive analysis of Lymphoma‐associated haemophagocytic syndrome in a large French multicentre cohort detects some clues to improve prognosis
Authors: Bigenwald Camille , Fardet Laurence , Coppo Paul , Meignin Véronique , Lazure Thierry , Fabiani Bettina , Kohn Milena , Oksenhendler Eric , Boutboul David , Uzzan Mathieu , Lambotte Olivier , Galicier Lionel
Published: July 2018

Lymphoma‐associated haemophagocytic syndrome (LAHS) accounts for most cases of secondary haemophagocytic syndrome (HS) and has been extensively described in Asian populations. However, little is known about the epidemiology of LAHS in Western countries. We herein report a case series of 71 LAHS patients in which the lymphomas were mainly of the aggressive type. Diagnoses included non‐Hodgkin B cell lymphoma (46·5%) including human herpes virus 8‐associated non‐Hodgkin lymphoma (12·7%), T cell lymphoma (28·2%) and Hodgkin lymphoma (23·9%). An underlying immunodeficiency was described in 30 patients (42·3%). Early mortality within the 30 days following HS diagnosis was observed in 26·8% of cases. The overall survival was estimated at 45·7% [95% confidence interval, CI (35·4–59·0)] at 6 months, and 34·3% [95% CI (24·8–47·4)] at 2 years. Concurrent infection, age over 50 years, ethnicity and etoposide treatment were independently associated with mortality. While it appears that certain types of lymphomas were more prone to trigger HS, LAHS were not restricted to a few types of lymphoma. The overall prognosis was poor, with a particularly high rate of early mortality, highlighting the importance of both early recognition and choice of initial therapeutic management.
Associations between maternal responsive linguistic input and child language performance at age 4 in a community‐based sample of slow‐to‐talk toddlers
Authors: Levickis Penny , Reilly Sheena , Girolametto Luigi , Ukoumunne Obioha C. , Wake Melissa
Published: July 2018

Background

In a community sample of slow‐to‐talk toddlers, we aimed to (a) quantify how well maternal responsive behaviors at age 2 years predict language ability at age 4 and (b) examine whether maternal responsive behaviors more accurately predict low language status at age 4 than does expressive vocabulary measured at age 2 years.

Design or Methods

Prospective community‐based longitudinal study. At child age 18 months, 1,138 parents completed a 100‐word expressive vocabulary checklist within a population survey; 251 (22.1%) children scored ≤20th percentile and were eligible for the current study. Potential predictors at 2 years were (a) responsive language behaviors derived from videotaped parent–child free‐play samples and (b) late‐talker status. Outcomes were (a) Clinical Evaluation of Language Fundamentals—Preschool Second Edition receptive and expressive language standard score at 4 years and (b) low language status (standard score > 1.25 standard deviations below the mean on expressive or receptive language).

Results

Two hundred eight (82.9% of 251) participants were retained to age 4. In adjusted linear regression analyses, maternal expansions predicted higher receptive (p < 0.001, partial R2 = 6.5%) and expressive (p < 0.001, partial R2 = 7.7%), whereas labels predicted lower receptive (p = 0.01, partial R2 = 2.8%) and expressive (p = 0.007, partial R2 = 3.5%) language scores at 4. The logistic regression model containing only responsive behaviors achieved “fair” predictive ability of low language status at age 4 (area under curve [AUC] = 0.79), slightly better than the model containing only late‐talker status (AUC = 0.74). This improved to “good” predictive ability with inclusion of other known risk factors (AUC = 0.82).

Conclusion

A combination of short measures of different dimensions, such as parent responsive behaviors, in addition to a child's earlier language skills increases the ability to predict language outcomes at age 4 to a precision that is approaching clinical value. Research to further enhance predictive values should be a priority, enabling health professionals to identify which slow‐to‐talk toddlers most likely will or will not experience later poorer language.
Enhanced TLR2 responses in multiple sclerosis
Authors: Fujiwara M , Anstadt E J , Flynn B , Morse K , Ng C , Paczkowski P , Zhou J , Mackay S , Wasko N , Nichols F , Clark R B
Published: July 2018

The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome-derived Toll-like receptor (TLR)2-stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof-of-concept, we reported that decreasing systemic TLR2 responsiveness by administering very low-dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll-like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system-targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing–remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS.
Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome
Authors: Ribeiro Cavalari Emanuela M. , de Paula Marcela P. , Arruda Mariana , Carraro Nathália , Martins Arthur , de Souza Kamila , Coelho Maria C. , de Oliveira e Silva de Morais Nathalie Anne , Moraes Aline B. , Vieira Neto Leonardo
Published: July 2018

Context

Although metabolic syndrome has been studied in patients with autonomous cortisol secretion, there are limited data for those with nonfunctioning adrenal incidentaloma (NFAI).

Objective

To assess metabolic syndrome frequency in NFAI patients and controls without adrenal adenoma according to World Health Organization (WHO), National Cholesterol Education Program‐Adult Treatment Panel III (NCEP‐ATP III), American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and International Diabetes Federation (IDF) criteria.

Design

Retrospective and transversal study.

Patients

Seventy‐four NFAI and 90 controls were evaluated. NFAI diagnosis was established according to current guidelines. The control group was selected based on normal adrenal imaging examinations.

Measurements

Subjects were categorized by metabolic syndrome presence according to WHO, NCEP‐ATP III, AACE/ACE and IDF.

Results

Age, gender, ethnicity, body mass index, smoking, menopause, statin and fibrate use were comparable between patients and controls. The frequency of prediabetes, dyslipidaemia and hypertension as well as waist circumference were significantly higher in the NFAI patients compared to the controls. The metabolic syndrome frequency in the NFAI group was significantly higher compared to the normal adrenal group: WHO: 69.2% × 31.0% (P < 0.001); NCEP‐ATP III: 81.7% × 44.9% (P < 0.001); AACE/ACE: 77.1% × 31.9% (P < 0.001); IDF: 78.6% × 45.5% (P < 0.001). Logistic regression analysis showed that NFAI was a predictor of metabolic syndrome according to WHO (P = 0.001), NCEP‐ATP III (P = 0.005) and AACE/ACE (P = 0.007).

Conclusions

Metabolic syndrome is frequently found in patients with NFAI, and this frequency is higher in NFAI patients than in those with normal adrenal imaging.
Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation
Authors: Xu Wen‐Xiao , Yu Jin‐Ling , Feng Yan , Yan Qiu‐Xin , Li Xin‐Yu , Li Ying , Liu Zhuo , Wang Di , Sun Xun , Li Ke‐Xin , Wang Lu‐Qi , Qiao Guo‐Fen , Li Bai‐Yan
Published: July 2018

Aim

To study the dominant role of parasympathetic inputs at cellular level of baroreflex afferent pathway and underlying mechanism in neurocontrol of blood pressure regulation.

Methods

Whole‐cell patch‐clamp and animal study were conducted.

Results

For the first time, we demonstrated the spontaneous activities from resting membrane potential in myelinated A‐ and Ah‐type baroreceptor neurons (BRNs, the 1st‐order), but not in unmyelinated C‐types, using vagus‐nodose slice of adult female rats. These data were further supported by the notion that the spontaneous synaptic currents could only be seen in the pharmacologically and electrophysiologically defined myelinated A‐ and Ah‐type baroreceptive neurons (the 2nd‐order) of NTS using brainstem slice of adult female rats. The greater frequency and the larger amplitude of the spontaneous excitatory postsynaptic currents (EPSCs) compared with the inhibitory postsynaptic currents (IPSCs) were only observed in Ah‐types. The ratio of EPSCs:IPSCs was estimated at 3:1 and higher. These results confirmed that the afferent‐specific spontaneous activities were generated from baroreflex afferent pathway in female‐specific subpopulation of myelinated Ah‐type BRNs in nodose and baroreceptive neurons in NTS, which provided a novel insight into the dominant role of sex‐specific baroreflex‐evoked parasympathetic drives in retaining a stable and lower blood pressure status in healthy subjects, particularly in females.

Conclusion

The data from current investigations establish a new concept for the role of Ah‐type baroreceptor/baroreceptive neurons in controlling blood pressure stability and provide a new pathway for pharmacological intervention for hypertension and cardiovascular diseases.