bluuebunny/crossref_metadata_2025 huggingface dataset:
Instability of MHD couette flow of an electrically conducting fluid
Authors: Hussain Zakir , Hussain Sultan , Kong Tiantian , Liu Zhou
Published: October 2018

We study the electrically conducting fluid stability of magnetohydrodynamic flow between parallel plates by Chebyshev collocation method by applied transverse magnetic field. Temporal growth is obtained by the governing equations. The results show that the dominating factor is the change in shape of the undisturbed velocity profile caused by the magnetic field, which depends only on the Hartmann number. The stability equations is solved by QZ-algorithm to find the eigenvalue problem. The numerical calculation show that Magnetic field with particular magnitude destabilizes Couette flow while other magnitude stabilize the flow. It is also analyzed that Rec decreases rapidly to the minimum value for Hartmann number Ha greater than 3.887 and increases steadily from Hartmann number Ha (>5.559). It is observed that critical Reynolds number Rec is larger as Hartmann number decreases from Ha=3.887. The two critical Reynolds numbers in the elliptic curves are found for different values of Hartmann number.
Selection and gene flow shape genomic islands that control floral guides
Authors: Tavares Hugo , Whibley Annabel , Field David L. , Bradley Desmond , Couchman Matthew , Copsey Lucy , Elleouet Joane , Burrus Monique , Andalo Christophe , Li Miaomiao , Li Qun , Xue Yongbiao , Rebocho Alexandra B. , Barton Nicolas H. , Coen Enrico
Published: October 2018

Significance

Populations often show “islands of divergence” in the genome. Analysis of divergence between subspecies of
Antirrhinum
that differ in flower color patterns shows that sharp peaks in relative divergence occur at two causal loci. The island is shaped by a combination of gene flow and multiple selective sweeps, showing how divergence and barriers between populations can arise and be maintained.
Bottom trawl fishing footprints on the world’s continental shelves
Authors: Amoroso Ricardo O. , Pitcher C. Roland , Rijnsdorp Adriaan D. , McConnaughey Robert A. , Parma Ana M. , Suuronen Petri , Eigaard Ole R. , Bastardie Francois , Hintzen Niels T. , Althaus Franziska , Baird Susan Jane , Black Jenny , Buhl-Mortensen Lene , Campbell Alexander B. , Catarino Rui , Collie Jeremy , Cowan James H. , Durholtz Deon , Engstrom Nadia , Fairweather Tracey P. , Fock Heino O. , Ford Richard , Gálvez Patricio A. , Gerritsen Hans , Góngora María Eva , González Jessica A. , Hiddink Jan G. , Hughes Kathryn M. , Intelmann Steven S. , Jenkins Chris , Jonsson Patrik , Kainge Paulus , Kangas Mervi , Kathena Johannes N. , Kavadas Stefanos , Leslie Rob W. , Lewis Steve G. , Lundy Mathieu , Makin David , Martin Julie , Mazor Tessa , Gonzalez-Mirelis Genoveva , Newman Stephen J. , Papadopoulou Nadia , Posen Paulette E. , Rochester Wayne , Russo Tommaso , Sala Antonello , Semmens Jayson M. , Silva Cristina , Tsolos Angelo , Vanelslander Bart , Wakefield Corey B. , Wood Brent A. , Hilborn Ray , Kaiser Michel J. , Jennings Simon
Published: October 2018

Significance

We conducted a systematic, high-resolution analysis of bottom trawl fishing footprints for 24 regions on continental shelves and slopes of five continents and New Zealand. The proportion of seabed trawled varied >200-fold among regions (from 0.4 to 80.7% of area to a depth of 1,000 m). Within 18 regions, more than two-thirds of seabed area remained untrawled during study periods of 2–6 years. Relationships between metrics of total trawling activity and footprint were strong and positive, providing a method to estimate trawling footprints for regions where high-resolution data are not available. Trawling footprints were generally smaller in regions where fisheries met targets for exploitation rates, implying collateral environmental benefits of effective fisheries management.
Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation
Authors: Xu Ran , Xu Yixi , Huo Wei , Lv Zhicong , Yuan Jingsong , Ning Shaokai , Wang Qingsong , Hou Mei , Gao Ge , Ji Jianguo , Chen Junjie , Guo Rong , Xu Dongyi
Published: October 2018

Significance

The Mre11–Rad50–Nbs1 (MRN) complex is well known for participating in DNA damage response pathways and mediating the ATM-dependent phosphorylation signaling cascade. Hypomorphic mutations in the human MRN complex have been identified in autosomal recessive genetic diseases, ataxia-telangiectasia–like disorder, and Nijmegen breakage syndrome. Here, we show that MRN forms a mitosis-specific complex with a protein, MMAP, which mediates a mitotic signaling cascade between PLK1 and KIF2A. We demonstrate that the assembly of this complex is crucial for normal spindle dynamics during mitosis. Thus, our study describes a signaling cascade in which PLK1-dependent phosphorylation promotes the assembly of the MRN–MMAP–PLK1–KIF2A complex, leading to mitotic spindle turnover and chromosome alignment.
Reducing dynamin 2 (DNM2) rescues
DNM2
-related dominant centronuclear myopathy
Authors: Buono Suzie , Ross Jacob A. , Tasfaout Hichem , Levy Yotam , Kretz Christine , Tayefeh Leighla , Matson John , Guo Shuling , Kessler Pascal , Monia Brett P. , Bitoun Marc , Ochala Julien , Laporte Jocelyn , Cowling Belinda S.
Published: October 2018

Significance

Centronuclear myopathies are rare and severe congenital muscle diseases. Here we hypothesized that reducing dynamin 2 (DNM2) may rescue the pathophysiology observed in
DNM2
-related dominant centronuclear myopathy. The total DNM2 expression was reduced in a faithful murine model (
Dnm2
RW/+
mice) using two different methods targeting both mutated and wild-type
Dnm2
, adeno-associated virus-shRNA, or antisense oligonucleotides, leading to a restoration of muscle mass, histopathology, and muscle ultrastructural features to wild-type levels. This provides a therapeutic strategy for treating this disease. We also propose that targeting both alleles in dominant diseases due to a mutation in only one of the alleles can successfully rescue the phenotypes.
Swi5–Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51 dissociation
Authors: Lu Chih-Hao , Yeh Hsin-Yi , Su Guan-Chin , Ito Kentaro , Kurokawa Yumiko , Iwasaki Hiroshi , Chi Peter , Li Hung-Wen
Published: October 2018

Significance

In DNA homologous recombination, recombinase-coated single-stranded DNA filament formation is the first committed step and is subject to tight regulation. Stabilization of nucleoprotein filament by accessory proteins can be achieved by enhancing filament formation, reducing filament disassembly, or both. However, the mechanism of regulation is not understood by conventional biochemical methods. This is a study of the mechanism of how accessory proteins stimulate filament assembly by applying single-molecule methods that allow us to monitor the binding of Rad51 on DNA in mouse and fission yeast. Our results show that the Swi5–Sfr1 complex demonstrates the evolutionarily conserved stimulation of Rad51 filament assembly by stabilizing Rad51 on DNA, allowing both the formation of the stable nucleus and the reduction of Rad51 dissociation.
Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations
Authors: Rivas-Carrillo Salvador Daniel , Pettersson Mats E. , Rubin Carl-Johan , Jern Patric
Published: October 2018

Significance

Retroviruses have invaded vertebrate hosts during millions of years by occasional germline infections, which were transmitted to the host offspring through generations as inherited endogenous retroviruses (ERVs). Thus, ERVs provide a remarkable record of virus–host interactions. State-of-the-art sequencing methods facilitate ERV identification to decipher their long-term associations with host species. By expanding the scope beyond presence or absence in a single reference genome assembly, it is possible to estimate ERV frequencies and spread in related wild and domestic host populations. Here we demonstrate a considerable ERV makeup variance in wild and domestic rabbit populations, which offers insights into retrovirus–host coevolution and an extension to common strategies in population comparative genomics.
Language policy, language study, and heritage language education in the U.S.
Authors: King Kendall A. , Liu Mengying , Schwedhelm María Cecilia
Published: October 2018

Language policy and language study in the U.S. have long been defined by three trends: an absence of national-level language policy; a highly multilingual history characterized by overwhelming shift towards English; and a tendency for educational policy to shift students rapidly towards English monolingualism, with students later needing to relearn these same, now ‘foreign’ languages in high school or university, resulting in dismally low proficiency levels. This chapter briefly considers these contradictions, all of which rest on pervasive ideologies of monolingualism and result in the tremendous squandering of linguistic riches. The chapter then offers examples of how language policy and language study play out in three very different heritage language learning contexts in the U.S., each focusing on a different type of language learner, language, and language policy. These include assessment and learning of Spanish among heritage speakers; language revitalization of Indigenous languages, and the teaching and learning in Chinese in community school contexts. We close by considering ongoing challenges to language study in the U.S., including teacher training and curriculum development.
L3, the tertiary language
Authors: Hammarberg Björn
Published: October 2018

The fact that learners of a new language often already have experience of one or more other non-native languages has come into focus with the growing interest in multilingualism as a linguistic phenomenon and multilingual education as a practical concern. Third language or L3 has become a regular term fairly recently in dealing with the complex constellations of languages that occur with multilingual speakers and exploring the roles of these languages in the acquisition process. The purpose of the present chapter is to examine and discuss the construct of L3 in the context of the individual speaker’s multilingual repertoire and language learning. I first touch upon the wide occurrence of bi- and multilingualism in the world of today, especially as promoted by globalization and modern communication technology, and individual multilingualism (plurilingualism) as the normal form of linguistic competence that develops in human speakers. I then discuss the speaker/learner’s linguistic repertoire as a dynamic complex system, as well as the mutual connection between the developing repertoire and the process of language use and acquisition in specific situations in time. What we mean by L3 is seldom reflected on in the literature on so-called third language acquisition (TLA). In defining L3, we should ask what kind of concept we need in order to represent a speaker’s non-first non-native language. It should be a concept which is cognitively grounded and compatible with the terms L1 and L2 as these are commonly used in SLA studies. This leads to a definition of L3 and a discussion of its cognitive role as “tertiary” in relation to pre-existing L1s and L2s. Cross-linguistic influence becomes more complex when more background languages than a single L1 are involved, since both L1s and L2s can become activated in the process. Recent literature has explored a range of factors that may determine which language will dominate as source language when acquiring an L3, and formed conflicting hypotheses regarding their relative strength. I examine some problems that are reflected in this research, including the “L2 status issue”. This has implications for understanding the potential benefit of a multilingual language background in language learning.
Affordances of multilingual learning situations – Possibilities and constraints for foreign language classrooms
Authors: Buendgens-Kosten Judith , Elsner Daniela
Published: October 2018

Against the background of technological development and linguistic diversity in our society, a multilingual software application for classroom usage, including digital picture-books in different languages, has been developed in the context of an EU-funded project called MuViT. This product has been adapted for a research study called LIKE (Elsner, Buendgens-Kosten & Hardy 2014) which focuses on the question how mono- and multilingual learners of English at primary and early secondary school level make use of different languages (L1, L2, L3) while working with a computer-based story in pairs. So far 50 dyads have been tested and observed during their work with the stories. In this paper, the relevant design decisions regarding the use of the multilingual digital storybooks and its implementation in a quasi-experimental setting will be discussed, focusing on the affordances they provide from the perspective of the researchers. In a second step, the focus will move to how pupils make use of the multilingual affordances offered by the learning environment (software and peer to peer situation). Case analyses drawn from the sample will be presented with regard to pupils’ receptive code-switching behavior. On the basis of a sequential qualitative analysis, we will describe in which way the use of different languages may contribute to or rather interfere with processes of foreign language learning. This analysis will point out the potential and limits of multilingual language learning environments (learning material and multilingual pair-/group work) with regard to foreign language learning and allow for methodological implications for the use of multilingual learning material and pair-/group work arrangements.
L1 effects in the early L3 acquisition of vocabulary and grammar
Authors: Hopp Holger , Kieseier Teresa , Vogelbacher Markus , Thoma Dieter
Published: October 2018

This chapter explores cross-linguistic influences in the lexical and grammatical acquisition of L3 English among child L2 learners of German with a variety of L1 backgrounds. For lexical development, we find interrelations in vocabulary size between L1, L2 and English lexicons. For grammar, a sentence repetition task does not show any differences between learner groups. Instead, all learners transfer German word order to English, irrespective of the properties of the L1 grammar. We discuss these findings in the context of current formal approaches to transfer in L3 acquisition and sketch some implications for foreign language teaching in a multilingual classroom.
Diversity, Ability, and Expertise in Epistemic Communities
Authors: Grim Patrick , Singer Daniel J. , Bramson Aaron , Holman Bennett , McGeehan Sean , Berger William J.
Published: October 2018

The Hong and Page ‘diversity trumps ability’ result has been used to argue for the more general claim that a diverse set of agents is epistemically superior to a comparable group of experts. Here we extend Hong and Page’s model to landscapes of different degrees of randomness and demonstrate the sensitivity of the ‘diversity trumps ability’ result. This analysis offers a more nuanced picture of how diversity, ability, and expertise may relate. Although models of this sort can indeed be suggestive for diversity policies, we advise against interpreting such results overly broadly.
LION LBD: a literature-based discovery system for cancer biology
Authors: Pyysalo Sampo , Baker Simon , Ali Imran , Haselwimmer Stefan , Shah Tejas , Young Andrew , Guo Yufan , Högberg Johan , Stenius Ulla , Narita Masashi , Korhonen Anna
Published: October 2018

Motivation

The overwhelming size and rapid growth of the biomedical literature make it impossible for scientists to read all studies related to their work, potentially leading to missed connections and wasted time and resources. Literature-based discovery (LBD) aims to alleviate these issues by identifying implicit links between disjoint parts of the literature. While LBD has been studied in depth since its introduction three decades ago, there has been limited work making use of recent advances in biomedical text processing methods in LBD.

Results

We present LION LBD, a literature-based discovery system that enables researchers to navigate published information and supports hypothesis generation and testing. The system is built with a particular focus on the molecular biology of cancer using state-of-the-art machine learning and natural language processing methods, including named entity recognition and grounding to domain ontologies covering a wide range of entity types and a novel approach to detecting references to the hallmarks of cancer in text. LION LBD implements a broad selection of co-occurrence based metrics for analyzing the strength of entity associations, and its design allows real-time search to discover indirect associations between entities in a database of tens of millions of publications while preserving the ability of users to explore each mention in its original context in the literature. Evaluations of the system demonstrate its ability to identify undiscovered links and rank relevant concepts highly among potential connections.

Availability and implementation

The LION LBD system is available via a web-based user interface and a programmable API, and all components of the system are made available under open licenses from the project home page http://lbd.lionproject.net.

Supplementary information

Supplementary data are available at Bioinformatics online.
Pisces: an accurate and versatile variant caller for somatic and germline next-generation sequencing data
Authors: Dunn Tamsen , Berry Gwenn , Emig-Agius Dorothea , Jiang Yu , Lei Serena , Iyer Anita , Udar Nitin , Chuang Han-Yu , Hegarty Jeff , Dickover Michael , Klotzle Brandy , Robbins Justin , Bibikova Marina , Peeters Marc , Strömberg Michael
Published: October 2018

Motivation

Next-generation sequencing technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants.

Results

We have developed Pisces, a rapid, versatile and accurate small-variant calling suite designed for somatic and germline amplicon sequencing applications. Accuracy is achieved by four distinct modules, each incorporating a number of novel algorithmic strategies.

Availability and implementation

Pisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces. Pisces is available on the BaseSpace™ SequenceHub. It is distributed on Illumina sequencing platforms such as the MiSeq™ and is included in the Praxis™ Extended RAS Panel test which was recently approved by the FDA.

Supplementary information

Supplementary data are available at Bioinformatics online.
TEPIC 2—an extended framework for transcription factor binding prediction and integrative epigenomic analysis
Authors: Schmidt Florian , Kern Fabian , Ebert Peter , Baumgarten Nina , Schulz Marcel H
Published: October 2018

Prediction of transcription factor (TF) binding from epigenetics data and integrative analysis thereof are challenging. Here, we present TEPIC 2 a framework allowing for fast, accurate and versatile prediction, and analysis of TF binding from epigenetics data: it supports 30 species with binding motifs, computes TF gene and scores up to two orders of magnitude faster than before due to improved implementation, and offers easy-to-use machine learning pipelines for integrated analysis of TF binding predictions with gene expression data allowing the identification of important TFs.

Availability and implementation

TEPIC is implemented in C++, R, and Python. It is freely available at https://github.com/SchulzLab/TEPIC and can be used on Linux based systems.

Supplementary information

Supplementary data are available at Bioinformatics online.
The role of intangible assets in explaining the investment–profit puzzle
Authors: Orhangazi Özgür
Published: October 2018

Starting around the early 2000s, and especially after the 2008 crisis, the rate of capital accumulation for US nonfinancial corporations has slowed down despite relatively high profitability; indicating a weakening of the link between profitability and investment. While the literature mostly focuses on financialisation and globalisation as the reasons behind this slowdown, I suggest adding another layer to these explanations and argue that, in conjunction with financialisation and globalisation, we need to pay attention to the increased use of intangible assets by nonfinancial corporations in the last two decades. Intangibles such as brand names, trademarks, patents and copyrights play a role in the widening of the profit–investment gap as the use of these assets enables firms to increase market power and profitability without necessarily generating a corresponding increase in fixed capital investment. After discussing the ways nonfinancial corporations use intangible assets, I look at large corporations in the USA and find the following: (i) The ratio of intangible assets to the capital stock increased in general. This increase is highest for firms in high-technology, healthcare, nondurables and telecommunications. (ii) Industries with higher intangible asset ratios have lower investment to profit ratios. (iii) Industries with higher intangible asset ratios have higher markups and profitability. (iv) The composition of the nonfinancial corporate sector has changed and the weight of high-technology and healthcare firms has increased; but this increase did not correspond to an equal increase in their investment share. The decline in the investment share of durables, nondurables and machinery is matched by an increase in the investment share of location-specific industries with low intangible asset use, most notably firms in energy extraction. In general, these firms have steadier markups and higher investment to profit ratios. (v) Yet, intangible-intensive industries’ profitability has increased faster than their share of investment or total assets. All in all, these findings are in line with the suggestion that the increased use of intangible assets enables firms to have high profitability without a corresponding increase in investment.
Temporal trends in adoption and outcomes of transcatheter aortic valve implantation: a SwissTAVI Registry analysis
Authors: Stortecky Stefan , Franzone Anna , Heg Dik , Tueller David , Noble Stephane , Pilgrim Thomas , Jeger Raban , Toggweiler Stefan , Ferrari Enrico , Nietlispach Fabian , Taramasso Maurizio , Maisano Francesco , Grünenfelder Jürg , Muller Olivier , Huber Christoph , Roffi Marco , Carrel Thierry , Wenaweser Peter , Windecker Stephan
Published: October 2018

Aims

To describe temporal trends in adoption and performance of transcatheter aortic valve implantation (TAVI) in Switzerland over a period of 5 years.

Methods and results

Between 2011 and 2015, a total of 3493 patients were consecutively included in the SwissTAVI Registry (NCT01368250) and analysed for the purpose of this study. The primary outcome measure was all-cause mortality at 1 year after TAVI. Over the 5-year period, a six-fold increase in the number of procedures was observed, whereas the baseline surgical risk estimated by the Society of Thoracic Surgeon (STS) score declined (from 6.8 ± 4.4% to 4.6 ± 3.6, P < 0.001). Overall, 1-year mortality amounted to 12.8%; mortality was highest in the first annual cohorts (14.6%, 14.8%, and 15.9% in 2011, 2012, and 2013, respectively) and decreased to 13.4% in 2014 and 9.7% in 2015. While rates of cerebrovascular events, peri-procedural myocardial infarction, moderate/severe paravalvular regurgitation, and Stage 3 acute kidney injury did not significantly change over time, a significant reduction in life threatening or major bleeding was noted at 30-day follow-up during the latest compared with earlier years of recruitment.

Conclusion

This long-term recruitment analysis of a national TAVI registry showed rapid adoption paralleled by a progressive decrease of patients’ baseline risk profile. Early and late survival significantly improved over time as did the rate of life threatening or major bleeding.
Infant nutrition and growth: trends and inequalities in four population-based birth cohorts in Pelotas, Brazil, 1982–2015
Authors: Gonçalves Helen , Barros Fernando C , Buffarini Romina , Horta Bernardo L , Menezes Ana M B , Barros Aluísio J D , Domingues Marlos R , Victora Cesar G ,   Pelotas Cohorts Study Group, Matijasevich Alicia , Bertoldi Andrea Dãmaso , Bassani Diego G , Wehrmeister Fernando C , Santos Iná S , Murray Joseph , Tovo-Rodrigues Luciana , Assunção Maria Cecilia F , Silveira Mariangela F , Hallal Pedro R C
Published: October 2018

Background

Levels of child undernutrition have declined in many middle-income countries, whereas overweight and obesity have increased. We describe time trends in nutritional indicators at age 1 year in the 1982, 1993, 2004 and 2015 Pelotas (Brazil) Birth Cohorts.

Methods

Each study included all children born in the urban area of the city, with over 4 200 births in each cohort. Children were measured at approximately 12 months of age. Anthropometric indicators were calculated according to World Health Organization Growth Standards. Stunting and wasting were defined as <-2 Z scores for length for age and weight for length, and overweight as >2 Z scores for weight for length. Prevalence was stratified by sex, maternal skin colour and family income.

Results

The prevalence of stunting declined by 53% (from 8.3% to 3.9%) from 1982 to 2015. Wasting prevalence remained stable at low levels (1.8% in 1982 and 1.7% in 2015), whereas overweight increased by 88% (6.5% to 12.2%). Undernutrition was more common among boys, those born to mothers with brown or black skin colour and in the poorest quintile of families. Socioeconomic inequalities in undernutrition decreased markedly over time. Overweight was markedly more common among the rich in 1982, but fast increase among the poor eliminated socioeconomic differences by 2015, when all groups showed similar prevalence.

Conclusions

Our results confirm the rapid nutrition transition in Brazil, with marked reduction in levels and inequalities in undernutrition in parallel with a rapid increase in overweight, which became the main nutritional problem for children.
Cranky comments: detecting clinical decision support malfunctions through free-text override reasons
Authors: Aaron Skye , McEvoy Dustin S , Ray Soumi , Hickman Thu-Trang T , Wright Adam
Published: October 2018

Background

Rule-base clinical decision support alerts are known to malfunction, but tools for discovering malfunctions are limited.

Objective

Investigate whether user override comments can be used to discover malfunctions.

Methods

We manually classified all rules in our database with at least 10 override comments into 3 categories based on a sample of override comments: “broken,” “not broken, but could be improved,” and “not broken.” We used 3 methods (frequency of comments, cranky word list heuristic, and a Naïve Bayes classifier trained on a sample of comments) to automatically rank rules based on features of their override comments. We evaluated each ranking using the manual classification as truth.

Results

Of the rules investigated, 62 were broken, 13 could be improved, and the remaining 45 were not broken. Frequency of comments performed worse than a random ranking, with precision at 20 of 8 and AUC = 0.487. The cranky comments heuristic performed better with precision at 20 of 16 and AUC = 0.723. The Naïve Bayes classifier had precision at 20 of 17 and AUC = 0.738.

Discussion

Override comments uncovered malfunctions in 26% of all rules active in our system. This is a lower bound on total malfunctions and much higher than expected. Even for low-resource organizations, reviewing comments identified by the cranky word list heuristic may be an effective and feasible way of finding broken alerts.

Conclusion

Override comments are a rich data source for finding alerts that are broken or could be improved. If possible, we recommend monitoring all override comments on a regular basis.
Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol
Authors: Evenepoel Pieter , Claes Kathleen , Meijers Björn , Laurent Michaël R , Bammens Bert , Naesens Maarten , Sprangers Ben , Cavalier Etienne , Kuypers Dirk
Published: October 2018

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median −2.2% [interquartile range (IQR) −5.9–1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR −3.2–7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.
Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis
Authors: Coppo Rosanna
Published: October 2018

The search of personalized treatment for a subject with immunoglobulin A nephropathy (IgAN) is appealing since the individual long-term outcome is highly variable in spite of common mild clinical signs such as microscopic haematuria, moderate proteinuria and slightly reduced glomerular filtration rate (GFR). The only risk factor considered by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines to target corticosteroid/immunosuppressive treatment in IgAN is proteinuria persistently >1 g/day despite 3–6 months of optimized supportive care. However, proteinuria in IgAN may result not only from active lesions but also from sclerotic glomerular lesions with hyperfiltration and tubular damage. The Oxford classification study and subsequent investigations have indicated the value of pathology risk factors for progression independent of proteinuria, blood pressure and GFR at renal biopsy. Meanwhile new studies have provided an improved understanding of the pathogenetic mechanisms operating in IgAN leading to kidney tissue damage. These findings suggest the possibility for the individual patient with IgAN of using a pathology-based therapy, taking into consideration the pathogenetic mechanisms operating at the time of renal biopsy. This review is largely opinion based, since evidence-based reports are mostly incomplete: hypotheses are suggested based on interesting published investigations. The clinician faces a daily challenge: find the best management for his/her patient, modelling a rather general indication as obtained by the guidelines to the needs of the patient. This review offers some considerations that hopefully will be useful in this difficult choice.
Neurosurgery and Manned Spaceflight
Authors: Panesar Sandip S , Fernandez-Miranda Juan C , Kliot Michel , Ashkan Keyoumars
Published: October 2018

There has been a renewed interest in manned spaceflight due to endeavors by private and government agencies. Publicized goals include manned trips to or colonization of Mars. These missions will likely be of long duration, exceeding existing records for human exposure to extra-terrestrial conditions. Participants will be exposed to microgravity, temperature extremes, and radiation, all of which may adversely affect their physiology. Moreover, pathological mechanisms may differ from those of a terrestrial nature. Known central nervous system (CNS) changes occurring in space include rises in intracranial pressure and spinal unloading. Intracranial pressure increases are thought to occur due to cephalad re-distribution of body fluids secondary to microgravity exposure. Spinal unloading in microgravity results in potential degenerative changes to the bony vertebrae, intervertebral discs, and supportive musculature. These phenomena are poorly understood. Trauma is of highest concern due to its potential to seriously incapacitate crewmembers and compromise missions. Traumatic pathology may also be exacerbated in the setting of altered CNS physiology. Though there are no documented instances of CNS pathologies arising in space, existing diagnostic and treatment capabilities will be limited relative to those on Earth. In instances where neurosurgical intervention is required in space, it is not known whether open or endoscopic approaches are feasible. It is obvious that prevention of trauma and CNS pathology should be emphasized. Further research into neurosurgical pathology, its diagnosis, and treatment in space are required should exploratory or colonization missions be attempted.
Variability in Emergency Medicine Provider Decisions on Hospital Admission and Antibiotic Treatment in a Survey Study for Acute Bacterial Skin and Skin Structure Infections: Opportunities for Antimicrobial Stewardship Education
Authors: Almarzoky Abuhussain Safa S , Burak Michelle A , Adams Danyel K , Kohman Kelsey N , Tart Serina B , Hobbs Athena L V , Jacknin Gabrielle , Nailor Michael D , Keyloun Katelyn R , Nicolau David P , Kuti Joseph L
Published: October 2018

Background

Acute bacterial skin and skin structure infections (ABSSSIs) are a frequent cause of emergency department (ED) visits. Providers in the ED have many decisions to make during the initial treatment of ABSSSI. There are limited data on the patient factors that influence these provider decisions.

Methods

An anonymous survey was administered to providers at 6 EDs across the United States. The survey presented patient cases with ABSSSIs ≥75 cm2 and escalating clinical scenarios including relapse, controlled diabetes, and sepsis. For each case, participants were queried on their decision for admission vs discharge and antibiotic therapy (intravenous, oral, or both) and to rank the factors that influenced their antibiotic decision.

Results

The survey was completed by 130 providers. For simple ABSSSI, the majority of providers chose an oral antibiotic and discharged patients home. The presence of recurrence or controlled diabetes resulted in more variation in responses. Thirty-four (40%) and 51 (60%) providers chose intravenous followed by oral antibiotics and discharged the recurrence and diabetes cases, respectively. Presentation with sepsis resulted in initiation with intravenous antibiotics (122, 95.3%) and admission (125, 96.1%) in most responses.

Conclusions

Variability in responses to certain patient scenarios suggests opportunities for education of providers in the ED and the development of an ABSSSI clinical pathway to help guide treatment.
A Moso Bamboo Drought-Induced 19 Protein, PeDi19-4, Enhanced Drought and Salt Tolerance in Plants via the ABA-Dependent Signaling Pathway
Authors: Wu Min , Cai Ronghao , Liu Huanlong , Li Fei , Zhao Yang , Xiang Yan
Published: October 2018

Here, 10 drought-induced 19 (Di19) proteins from Phyllostachys edulis were analyzed and an important stress-related candidate gene (PeDi19-4) was isolated based on analysis of phylogenetic relationships and expression profiles. PeDi19-4 is a nuclear localization protein that can bind the conserved TACA(A/G)T sequence, as determined using enzyme-linked immunosorbent assay (EMSA). PeDi19-4 has no transcriptional activity in yeast but functions as a transcription activator in plants. Overexpression of PeDi19-4 in rice and Arabidopsis thaliana enhanced drought and salt tolerance as determined through phenotypic analysis and the use of stress-associated physiological indicators. PeDi19-4 transgenic plants showed increased sensitivity to ABA during seed germination and early seedling growth. Additionally, transgenic rice accumulated more ABA than wild-type plants under drought and salt stress conditions. Moreover, the stomata of PeDi19-4-overexpressing plants changed significantly with ABA treatment. RNA sequencing revealed that PeDi19-4 regulated the expression of a wide spectrum of stress-/ABA-responsive differentially expressed genes. The stress-responsive genes (OsZFP252 and OsNAC6) and ABA-responsive genes (OsBZ8 and OsbZIP23) were direct targets of PeDi19-4. Our research indicated that PeDi19-4 enhanced drought and salt tolerance in plants via the ABA-dependent signaling pathway.
MIND, Anti-Psychiatry, and the Case of the Mental Hygiene Movement’s ‘Discursive Transformation’
Authors: Toms Jonathan
Published: October 2018

During the 1970s the National Association for Mental Health (NAMH) re-labelled itself MIND, becoming a rights-based organisation, critiquing psychiatry and emphasising patients’ citizenship. Its transformation has been coloured by attributions of the influence of anti-psychiatry. This article argues that the relevance of anti-psychiatry has been over-simplified. It examines MIND’s history as part of the psychiatric strategy known as mental hygiene. This movement’s agenda can be understood as paradigmatic of much that anti-psychiatry renounced. However, building on the sociologist Nick Crossley’s description of the interactional nature of Social Movement Organisations in the psychiatric field, this article shows that a ‘discursive transformation’ can be deduced in core elements of mental hygienist thinking. This transformation of discourse clearly prefigured important elements of anti-psychiatry, and also fed into MIND’s rights approach. But it must be appreciated on its own terms. Its distinctiveness under MIND is shown in its application to people with learning disabilities.
The Host Stomatal Density Determines Resistance to Septoria gentianae in Japanese Gentian
Authors: Tateda Chika , Obara Kazue , Abe Yoshiko , Sekine Reiko , Nekoduka Syuuichi , Hikage Takashi , Nishihara Masahiro , Sekine Ken-Taro , Fujisaki Koki
Published: October 2018

Plant stomata represent the main battlefield for host plants and the pathogens that enter plant tissues via stomata. Septoria spp., a group of ascomycete fungi, use host plant stomata for invasion and cause serious damage to agricultural plants. There is no evidence, however, showing the involvement of stomata in defense systems against Septoria infection. In this study, we isolated Septoria gentianae 20-35 (Sg20-35) from Gentiana triflora showing gentian leaf blight disease symptoms in the field. Establishment of an infection system using gentian plants cultured in vitro enabled us to observe the Sg20-35 infection process and estimate its virulence in several gentian cultivars or lines. Sg20-35 also entered gentian tissues via stomata and showed increased virulence in G. triflora compared with G. scabra and their interspecific hybrid. Notably, the susceptibility of gentian cultivars to Sg20-35 was associated with their stomatal density on the adaxial but not abaxial leaf surface. Treatment of EPIDERMAL PATTERNING FACTOR-LIKE 9 (EPFL9/STOMAGEN) peptides, a small secreted peptide controlling stomatal density in Arabidopsis thaliana, increased stomatal density on the adaxial side of gentian leaves as well. Consequently, treated plants showed enhanced susceptibility to Sg20-35. These results indicate that stomatal density on the adaxial leaf surface is one of the major factors determining the susceptibility of gentian cultivars to S. gentianae and suggest that stomatal density control may represent an effective strategy to confer Septoria resistance.
Advances in site-specific gene editing for primary immune deficiencies
Authors: Kuo Caroline Y.
Published: October 2018

Purpose of review

Conventional gene therapy has been a successful, curative treatment modality for many primary immune deficiencies with significant improvements in the last decade. However, the risk of leukemic transformation with viral-mediated gene addition still remains, and unregulated gene addition is not an option for certain diseases in which the target gene is closely controlled. The recent bloom in genome modification platforms has created the opportunity to site-specifically correct mutated DNA base pairs or insert a corrective cDNA minigene while maintaining gene expression under control of endogenous regulatory elements.

Recent findings

There is an abundance of ongoing research utilizing programmable nucleases to facilitate site-specific gene correction of many primary immune deficiencies including X-linked severe combined immune deficiency, X-linked chronic granulomatous disease, Wiskott–Aldrich syndrome, X-linked hyper-IgM syndrome, X-linked agammaglobulinemia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked. In all, these studies have demonstrated the ability to integrate corrective DNA sequences at a precise location in the genome at rates likely to either cure or ameliorate disease.

Gene editing for primary immune deficiency (PID) has advanced to the point to that translation to clinical trials is likely to occur in the next several years. At the current pace of research in DNA repair mechanisms, stem cell biology, and genome-editing technology, targeted genome modification represents the next chapter of gene therapy for PID.
Very early onset IBD: novel genetic aetiologies
Authors: Batura Vritika , Muise Aleixo M.
Published: October 2018

Purpose of review

To summarize the current understanding and recent advances on the genetic aetiology in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD).

Recent findings

IBD is a chronic disorder of the gastrointestinal tract whose manifestation is a result of complex interactions between genetics, environment, immune system and microbial flora. Over 230 IBD risk loci have been reported in genome wide association studies but the genetic contribution of the majority of these loci in the manifestation of IBD is very low. Patients with VEO-IBD present with a more severe disease than older patients, characterized by poor prognosis and failure of conventional therapy. Recent studies have reported several monogenic diseases with high penetrance that present with IBD and IBD-like intestinal manifestations and overlap with primary immunodeficiencies. Increasing body of evidence supports a prominent role of genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD are reviewed and current challenges in therapy with potential strategy to manage the disease are discussed.

Functional analysis of the genes implicated in monogenic IBD has increased the understanding of the underlying pathobiological mechanism of the disease. This knowledge can be used to personalize medicine for specific patients, improving the standard of care and quality of life.
Delay in Hip Fracture Surgery Prolongs Postoperative Hospital Length of Stay but Does Not Adversely Affect Outcomes at 30 Days
Authors: Mitchell Sean M. , Chung Andrew S. , Walker Joseph B. , Hustedt Joshua W. , Russell George V. , Jones Clifford B.
Published: October 2018

Objectives:

To evaluate the association between the timing of hip fracture surgery with postoperative length of stay and outcomes.

Design:

Retrospective review using the American College of Surgeons National Surgical Quality Improvement Program database.

Setting:

National inquiry database incorporating 140 academic and private medical centers.

Patients:

Seventeen thousand four hundred fifty-nine patients who underwent surgery for a hip fracture between 2006 and 2013 were identified from the National Surgical Quality Improvement Program database.

Intervention:

Surgical management of hip fractures was performed at the discretion of participating surgeons.

Outcome Measure:

Thirty-day outcomes including postoperative length of stay, readmission rates, reoperation rates, complications, and mortality rates.

Results:

Of the 17,459 patients, 4107 (23.5%) were operated on within 24 hours, 8740 (50.1%) within 24–48 hours, and 4612 (26.4%) more than 48 hours after hospital admission. Increased time to surgery was associated with longer postoperative hospital length of stay. Prolonged time to surgery did not adversely affect postoperative outcomes.

Conclusions:

Although a delay in the management of hip fractures is associated with an increase in postoperative hospital length of stay, 30-day postoperative outcomes are not adversely affected in patients undergoing hip fracture fixation.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Far Cortical Locking Fixation of Distal Femur Fractures is Dominated by Shear at Clinically Relevant Bridge Spans
Authors: Habet Nahir , Elkins Jacob , Peindl Richard , Killen Cameron , Lack William D.
Published: October 2018

Objectives:

Far cortical locking (FCL) constructs have been shown to increase axial interfragmentary displacement while limiting shear and have been specifically recommended in the treatment of distal femur fractures. However, there is no available data regarding their mechanical behavior within the range of bridge spans typically used for comminuted distal femur fractures. This biomechanical study of distal femur locked plate fixation assessed 4 methods of diaphyseal fixation for associated axial and shear displacement at bridge spans typically used in clinical practice.

Methods:

Distal femur locking plates were used to bridge simulated fractures in femur surrogates with 4 different methods of diaphyseal fixation (bicortical locking, bicortical nonlocking, near cortical locking, and FCL). Axial and shear displacement were assessed at 5 different bridge spans for each fixation method.

Results:

Diaphyseal fixation type was associated with the amount of shear (P = 0.04), but not the amount of axial displacement (P = 0.39). Specifically, FCL constructs demonstrated greater shear than bicortical locking (median 4.57 vs. 2.94 mm, P = 0.02) and bicortical nonlocking (median 4.57 vs. 3.41 mm, P = 0.02) constructs.

Conclusions:

Unexpectedly, FCL constructs demonstrated greater shear than bicortical locking and nonlocking constructs and similar axial displacement for all fixation methods. Bridge span had a dominant effect on displacement that interacted negatively with more flexible FCL diaphyseal fixation. Potentially interactive construct features are best studied in concert. Given the complexity of these relationships, computational modeling will likely play an integral role in future mechanotransduction research.