bluuebunny/crossref_metadata_2025 huggingface dataset:
Forced vital capacity less than 1: A mark for high-risk patients
Authors: Warner Rachel , Knollinger Porter , Hobbs Gerald , Lilly Christa , Grabo Daniel , Wilson Alison
Published: April 2018

BACKGROUND

Rib fractures (RFx) continue to be a source of morbidity and mortality. A RFx care pathway has been used based on forced vital capacity (FVC). The objective of this study was to test the hypothesis that deterioration of FVC to less than 1 after admission is a marker for high-risk patients and affects outcomes.

METHODS

A retrospective study of patients enrolled in an RFx care pathway at a Level 1 trauma center from 2009 to 2014. All patients had an admission FVC greater than 1. 2 groups were analyzed: patients with a lowest inpatient FVC less than 1 (Group A) compared to patients with lowest inpatient FVC of 1 or greater (Group B). Complications [pneumonia, upgrade to the intensive care unit, readmission, and intubation] and demographics were examined. Patients without documented admission FVCs were excluded. p < 0.05 was considered significant.

RESULTS

A total of 1,106 patients were analyzed (Group A, 187; Group B, 919). Patients whose FVC dropped less than 1 (Group A) had a higher complication rate [15% (Group A) vs 3.2% (Group B); p < 0.001]. Rates of pneumonia, readmission, unplanned upgrade, and intubation were all significantly higher in Group A [pneumonia: 9% (Group A) vs 1.4% (Group B), p < 0.001; readmission: 4% (Group A) vs 1.7% (Group B), p = 0.04; upgrade; 3.7% (Group A) vs 0.2% (Group B), p < 0.001; intubation: 1.6% (Group A) vs 0.1% (Group B), p = 0.02]. Hospital length of stay was longer in Group A [10 days (Group A) vs 4 days (Group B), p < 0.001].

CONCLUSIONS

Forced vital capacity predicts complications in patients with RFx. Patients whose FVC falls less than 1 during admission are at high risk for pulmonary complications. Daily FVC testing for patients admitted with RFx can predict outcomes. Forced vital capacity less than 1 should be considered as a marker for complications. Once FVC drops less than 1, patients should be considered for increased interventions. Even if the patient has not yet clinically deteriorated, consideration for higher level of care is warranted.

LEVEL OF EVIDENCE

Prognostic study, level III.
Glycoprotein 3 of porcine reproductive and respiratory syndrome virus exhibits an unusual hairpin-like membrane topology
Authors: Zhang Minze , Krabben Ludwig , Wang Fangkun , Veit Michael
Published: April 2018

The glycoprotein GP3 of the Arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) consists of a cleaved signal peptide, a highly glycosylated domain, a short hydrophobic region and an unglycosylated C-terminal domain. GP3 is supposed to form a complex with GP2 and GP4 in virus particles, but secretion of GP3 from cells has also been reported.

We analyzed the membrane topology of GP3 from various PRRSV strains. A fraction of the protein is secreted from transfected cells; GP3 from PRRSV-1 strains to a greater extent than GP3 from PRRSV-2 strains. This secretion behavior is reversed after exchange of the variable C-terminal domain. A fluorescence protease protection assay shows that the C-terminus of GP3, fused to GFP, is resistant against proteolytic digestion in permeabilized cells. Furthermore, glycosylation sites inserted into the C-terminal part of GP3 are used. Both experiments indicate that the C-terminus of GP3 is translocated into the lumen of the endoplasmic reticulum. Deletion of the conserved hydrophobic region greatly enhances secretion of GP3 and fusion of this domain to GFP promotes membrane anchorage. Bioinformatics suggests that the hydrophobic region might form an amphipathic helix. Accordingly, exchanging only a few amino acids in its hydrophilic face prevents and in its hydrophobic face enhances secretion of GP3. Exchanging the latter amino acids in the context of the viral genome did not affect release of virions, but released particles were not infectious. In sum, GP3 exhibits an unusual hairpin-like membrane topology that might explain why a fraction of the protein is secreted.

IMPORTANCE

The porcine reproductive and respiratory syndrome virus (PRRSV) is the most important pathogen in the pork industry. It causes persistent infections that lead to reduced weight gain of piglets; highly pathogenic strains even kill 90% of an infected pig population. PRRSV cannot be eliminated from pig farms by vaccination due to the large amino acid variability between the existing strains, especially in the glycoproteins. Here we analyzed basic structural features of glycoprotein 3 (GP3) from various PRRSV strains. We show that the protein exhibits an unusual hairpin-like membrane topology; membrane anchoring might occur via an amphipathic helix. This rather weak membrane anchor explains why a fraction of the protein is secreted from cells. Interestingly, PRRSV-1 strains secrete more GP3 than PRRSV-2. We speculate that secreted GP3 might play a role during PRRSV infection of pigs; it might serve as a decoy to distract antibodies away from virus particles.
Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH
Authors: Liu Jian , Liu Luogen , Zeng Shinuan , Meng Xiaobin , Lei Nanfeng , Yang Hai , Li Runcai , Mu Xin , Guo Xuemin
Published: April 2018

Enterovirus 71 (EV71) is the common causative agent of hand-foot-mouth disease (HFMD). Despite evidence in mice model suggested that the interferon (IFN) signaling pathways play a role in defending against this virus, knowledge on the IFN-mediated antiviral response is still limited. Here we identified an IFN-stimulated gene (ISG) called L3HYPHD, whose expression inhibits EV71 replication. Mapping assay indicated that amino acids 61-120 and 295-354 are critical for its optimal antiviral activity. Mechanismly, L3HYPDH specifically inhibits protein translation mediated by EV71 internal ribosome entry site (IRES). Our data thus uncovered a new mechanism utilized by the host cell to restrict EV71 replication.
Effect of Infection with, and Treatment of, Sensitive and Resistant Strains of Teladorsagia Circumcincta on the Ovine Intestinal Microbiota
Authors: Watkins Craig A. , Bartley Dave J. , Ergün Burcu Gündüz , Yıldızhan Büşra , Ross-Watt Tracy , Morrison Alison A. , Rosales Sanmartín Maria J. , Strathdee Fiona , Andrews Leigh , Free Andrew
Published: April 2018

Nematodes are one of the main impactors on health, welfare and productivity of farmed animals. Teladorsagia circumcincta is arguably one of the most globally important nematode species in sheep. Control of these nematode infections is essential and heavily reliant on chemotherapy (anthelmintics), but this has been complicated by the development of anthelmintic resistance. In mammals the composition of the intestinal microbiota has been shown to have a significant effect on overall health. The interactions between host, microbiota and pathogens are complex and influenced by numerous factors. In this study, the interactions between T. circumcincta infections and microbial composition and abundance were investigated. In a preliminary study the intra-and inter-individual diversity and composition of the microbiota of grazing sheep was assessed in two distinct regions of the ovine intestinal tract, the terminal ileum (TI) and rectal contents. Additionally, the effects of experimental infection of sheep with two strains of T. circumcincta (anthelmintic resistant or sensitive) on the microbiota were assessed with and without anthelmintic (monepantel) administration. The inter-animal variability was greater in the TI compared to the rectal samples. However, the alpha-diversity (species richness) was significantly lower in the TI samples. In the experimental study, clear differences were observed between successfully treated animals and those sheep that were left untreated and/or those carrying resistant nematodes. Differences in microbiota between the four different experimental conditions were observed and potential predictive biomarkers were identified. In particular, a restoration of potentially beneficial Bifidobacteria sp. in successfully-treated animals was observed.
Unilateral movement preparation causes task-specific modulation of TMS responses in the passive, opposite limb
Authors: Chye Lilian , Riek Stephan , de Rugy Aymar , Carson Richard G. , Carroll Timothy J.
Published: April 2018

Corticospinal excitability is modulated for muscles on both sides of the body during unilateral movement preparation. For the effector, there is a progressive increase in excitability, and a shift in direction of muscle twitches evoked by transcranial magnetic stimulation (TMS) toward the impending movement. By contrast, the directional characteristics of excitability changes in the opposite (passive) limb have not been fully characterized. Here we assessed how preparation of voluntary forces towards four spatially distinct visual targets with the left wrist alters muscle twitches and motor evoked potentials (MEPs) elicited by TMS of left motor cortex. MEPs were facilitated significantly more in muscles homologous to agonist rather than antagonist muscles in the active limb, from 120 ms prior to voluntary EMG onset. Thus, unilateral motor preparation has a directionally-specific influence on pathways projecting to the opposite limb that corresponds to the active muscles rather than the direction of movement in space. The directions of TMS-evoked twitches also deviated toward the impending force direction of the active limb, according to muscle-based coordinates, following the onset of voluntary EMG. The data indicate that preparation of a unilateral movement increases task-dependent excitability in ipsilateral motor cortex, or its downstream projections, that reflect the forces applied by the active limb in an intrinsic (body-centered), rather than an extrinsic (world-centered), coordinate system. The results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.
Co-existing feedback loops generate tissue-specific circadian rhythms
Authors: Pett J. Patrick , Kondoff Matthew , Bordyugov Grigory , Kramer Achim , Herzel Hanspeter
Published: April 2018

Gene regulatory feedback loops generate autonomous circadian rhythms in mammalian tissues. The well-studied core clock network contains many negative and positive regulations. Multiple feedback loops have been discussed as primary rhythm generators but the design principles of the core clock and differences between tissues are still under debate.

Here we use global optimization techniques to fit mathematical models to circadian gene expression profiles for different mammalian tissues. It turns out that for every investigated tissue multiple model parameter sets reproduce the experimental data. We extract for all model versions the most essential feedback loops and find auto-inhibitions of Period and Cryptochrome genes, Bmal1/Rev-erb-α loops, and repressilator motifs as possible rhythm generators. Interestingly, the essential feedback loops differ between tissues, pointing to specific design principles within the hierarchy of mammalian tissue clocks. Self-inhibitions of Per and Cry genes are characteristic for models of SCN clocks, while in liver models many loops act in synergy and are connected by a repressilator motif. Tissue-specific use of a network of co-existing synergistic feedback loops could account for functional differences between organs.
The Hippo pathway effector Taz is required for cell fate specification and fertilization in zebrafish
Authors: Dingare Chaitanya , Niedzwetzki Alina , Klemmt Petra A , Godbersen Svenja , Fuentes Ricardo , Mullins Mary C. , Lecaudey Virginie
Published: April 2018

In the last decade, Hippo signaling has emerged as a critical pathway integrating extrinsic and intrinsic mechanical cues to regulate cell proliferation and survival, tissue morphology and organ size in vivo. Despite its essential role in organogenesis, surprisingly much less is known about how it connects biomechanical signals to control of cell fate and cell size during development. Here we unravel a novel and unexpected role of the Hippo pathway effector Taz (wwtr1) in the control of cell size and cell fate specification. In teleosts, fertilization occurs through a specific structure at the animal pole, called the micropyle. This opening in the chorion is formed during oogenesis by a specialized somatic follicle cell, the micropylar cell (MC). The MC has a peculiar shape and is much larger than its neighboring follicle cells but the mechanisms underlying its specification and cell shape acquisition are not known. Here we show that Taz is essential for the specification of the MC and subsequent micropyle formation in zebrafish. We identify Taz as the first bona fide MC marker and show that Taz is specifically and strongly enriched in the MC precursor before the cell can be identified morphologically. Altogether, our genetic data and molecular characterization of the MC lead us to propose that Taz is a key regulator of the MC fate activated by physical cues emanating from the oocyte to initiate the MC morphogenetic program. We describe here for the first time the mechanism underlying the specification of the MC fate.
A critical analysis of lifecycle models of the research process and research data management
Authors: Cox Andrew Martin , Tam Winnie Wan Ting
Published: April 2018

Purpose

Visualisations of research and research-related activities including research data management (RDM) as a lifecycle have proliferated in the last decade. The purpose of this paper is to offer a systematic analysis and critique of such models.

Design/methodology/approach

A framework for analysis synthesised from the literature presented and applied to nine examples.

Findings

The strengths of the lifecycle representation are to clarify stages in research and to capture key features of project-based research. Nevertheless, their weakness is that they typically mask various aspects of the complexity of research, constructing it as highly purposive, serial, uni-directional and occurring in a somewhat closed system. Other types of models such as spiral of knowledge creation or the data journey reveal other stories about research. It is suggested that we need to develop other metaphors and visualisations around research.

Research limitations/implications

The paper explores the strengths and weaknesses of the popular lifecycle model for research and RDM, and also considers alternative ways of representing them.

Practical implications

Librarians use lifecycle models to explain service offerings to users so the analysis will help them identify clearly the best type of representation for particular cases. The critique offered by the paper also reveals that because researchers do not necessarily identify with a lifecycle representation, alternative ways of representing research need to be developed.

Originality/value

The paper offers a systematic analysis of visualisations of research and RDM current in the Library and Information Studies literature revealing the strengths and weaknesses of the lifecycle metaphor.
Board involvement in corporate sustainability reporting: evidence from Sri Lanka
Authors: Rathnayaka Mudiyanselage Nayana Chandani Swarnapali
Published: April 2018

Purpose

The purpose of this paper is to explore the role played by the board of directors in corporate sustainability (CS) disclosure within the Asian context in which sustainability reporting (SR) is an emerging phenomenon.

Design/methodology/approach

Data are collected from a sample of 100 listed Sri Lankan companies over a period of four years (2012-2016), representing practically all the business sectors. This study draws on both agency and resource dependence theories, while binary logistic regression is performed for the data analysis.

Findings

The results point out that firms that follow a sustainability disclosure policy have larger boards, a higher proportion of independent directors and more female directors. Contrary to certain common assumptions, firms that practice sustainability disclosure are not influenced by dual leadership, board ethnicity and board ownership. This study helps firms to understand whether their boards can influence the sustainability disclosure choice or not and further, to validate the appropriateness of the agency theory and the resource dependence theory for examining issues of this nature.

Originality/value

This study contributes significantly to the extant literature on this subject by broadening the geographical coverage, which has generally been limited to the West in corporate disclosure studies.
Objective evaluation of fabric pilling based on data-driven visual attention model
Authors: Guan Shengqi , Li Wensen , Wang Jie , Lei Ming
Published: April 2018

Purpose

The purpose of this paper is to develop a new objective evaluation method of fabric pilling using data-driven visual attention model.

Design/methodology/approach

First, the multi-scale filtering images are formed by Gaussian pyramid decomposition. Second, center-surround differences algorithm is used between multi-scale filtering images to build saliency map. On this basis, the pilling information is segmented from saliency map by the segmentation threshold. Finally, the pilling is objectively evaluated by extracting pilling feature. Experimental result shows that compared with the traditional detection methods, the proposed objective evaluation method has strong anti-interference ability, and correct classification rate (CCR) is 96 percent.

Findings

Fabric pilling saliency can be effectively improved by data-driven visual attention model, which will lead to stronger anti-interference ability and higher correct classification rate.

Originality/value

To void uneven illumination, noise, and texture interference, the proposed method can enhance the saliency of small targets in saliency map using a bottom-up visual attention model. Through the threshold segmentation according to pilling feature, the pilling information is effectively from the fabric texture. Pilling feature about pilling area density is extracted to pilling grade evaluation.
Factors encouraging complete adoption of agricultural technologies
Authors: Khandker Varsha , Thakurata Indrajit
Published: April 2018

Purpose

Hybrid rice is considered as one of the technologies having the potential to push the production frontier to meet the growing demand for rice in India. The technology was introduced in India in 1994 but is yet to see widespread adoption. The purpose of this paper is to identify the factors that influence the partial/complete adoption of hybrid rice technology by the farmers in India. This study also assesses the factors behind difference in the share of land allocated to hybrid rice cultivation by farmers.

Design/methodology/approach

The study employs a Tobit model to evaluate the impact of factors related to technology, farmer, farm and geographical location on the decision to adopt hybrid rice. Data for this study are compiled from surveys of 441 hybrid rice growing farmers across 3 Indian states conducted during 2012-2013.

Findings

The paper finds that farmers with smaller landholdings, higher education and higher experience of growing hybrid rice are more likely to be complete adopters. Farmers reporting good demand for hybrid rice output and availability of subsidy on hybrid rice seeds also have higher probability of being complete adopters. However, the availability of hybrid rice seeds in government outlets and cultivating multiple kharif crops are negatively related to the extent of hybrid rice adoption. The results suggest insignificant impact of age, family size, ownership of cattle and machinery on the adoption level of hybrid rice by the farmers.

Research limitations/implications

Although the sample for this study has been collected from three states with different agro-climatic zones and productivity, the results cannot be generalized for other states.

Originality/value

There is a great potential to increase the area under hybrid rice cultivation in India. This study is one of the first attempts to look at the adoption levels of hybrid rice in India and determine the factors which might be hindering the complete adoption of the technology. Focusing on the factors positively related to complete adoption can help in enhancing the area under hybrid rice and similar approach can be used for other new agricultural technologies in the developing country context.
Potential impacts of desiccant-based drying and hermetic storage on the value chain for onion seeds in Nepal
Authors: Timsina Krishna P. , Bradford Kent J. , Dahal Peetambar , Shivakoti Ganesh P. , Kunusoth Keshavulu , Van Asbrouck Johan , Bajracharya Jwala , Pandey Indra Raj
Published: April 2018

Purpose

The purpose of this paper is to analyze the potential returns to value chain actors from employing desiccant bead drying and hermetic storage technology.

Design/methodology/approach

Information was collected from 175 different onion (Allium cepa L.) seed value chain actors in Nepal. Four different business models for the introduction of new bead drying and hermetic storage technology were compared to current practices through use of partial budgeting.

Findings

The increase in net income throughout the chain was quite similar in all four models, ranging from US$28.86 to 29.61 per kg of onion seed, making it difficult to say that any single model is best for all situations. However, there are differences in sharing of positive net income and negative net income for different actors in different models. Moreover, about US$5.85 million incremental return could be earned per year in Nepal from improved preservation of onion seed alone.

Research limitations/implications

This research assesses how to introduce a new technology, the dry chain concept to maintain seed quality, into the existing marketplace.

Originality/value

This paper focuses on the economics of a novel technology and compares different business models and scenarios.
Assessing competitive position of Uruguay’s beef sector
Authors: Lanfranco Bruno , Ferraro Bruno , Rava Catalina
Published: April 2018

Purpose

The purpose of this paper is to present an economic evaluation of Uruguay’s beef industry competitiveness to quantify the effects of public policies (taxes, subsidies, social charges) on the various links constituting the beef export chain and estimate the impact of transfers of resources between the beef industry and other sectors of the economy.

Design/methodology/approach

The Policy Analysis Matrix (PAM) techniques were employed to quantify the effects of public policies on the competitiveness of Uruguay’s beef industry. A series of PAM coefficients were calculated to assess the competitiveness of the beef export chain in 2010 and 2013 with comparison between the two years to make policy recommendations.

Findings

Beef sector returns captured by private agents decreased from 30 percent in 2010 to 10 percent in 2013. Competitiveness of the beef export chain deteriorated between 2010 and 2013 due primarily to higher prices paid for live cattle by the beef slaughtering, manufacturing, and packing sector. Uruguay’s beef industry transfers resources to the larger economy via social security payments and is penalized as a result of high capital costs.

Research limitations/implications

Although three different sources of resource transfers were identified, more effort is needed to improve the precision of estimations.

Originality/value

The competitiveness of export chains is critical to the economic and social wellbeing of small-economy countries. They must be efficient producing for the international markets at the time they constitute pillars of the whole economy.
The role of television in perceptions of dangerousness
Authors: Alexander Louise , Sheen Jade , Rinehart Nicole , Hay Margaret , Boyd Lee
Published: April 2018

Purpose

This critical review of historical and contemporary literature explores the role of television media in the prevalence of stigma towards persons experiencing a mental health challenge. In addition to this, the purpose of this paper is to examine the notion of perceived dangerousness, which is a concept where persons with mental illness are thought by others to be inherently dangerous.

Design/methodology/approach

A vigorous search of databases was undertaken for articles published between 2000 and 2016. Some seminal literature prior to 2000 was used to compare historical data with current literature. In total, 1,037 publications were reviewed against inclusion criteria.

Findings

While mental illness stigma has received much attention in the literature, television media and public perceptions of dangerousness have not. While these concepts are complex and multi-factorial, what we do understand is that approaches to address stigma have been largely unsuccessful, and that persons experiencing mental health challenges continue to be significantly disadvantaged.

Practical implications

Implications to practice for clinicians working in mental health on this issue have not been adequately explored within the literature. While media guidelines assist journalists to make informed choices when they portray mental health issues in television news, there are no such guidelines to inform drama television viewing.

Originality/value

Significantly, television’s role in perpetuation of perceptions of dangerousness has not been adequately explored as a combined co-occurring factor associated with the stigmatisation and avoidance of persons experiencing a mental health challenge. In an era when mental health challenges are on the rise, it is of great importance that we collectively seek to minimise negative impacts and improve the experiences of those with a mental health challenge through addressing stigma both individually and in television media.
Morphological analysis of legal ideology: locating interpretive divergence
Authors: Lees Emma , Shepherd Edward
Published: April 2018

Purpose

The purpose of this paper is to present a “manifesto” exploring a methodological approach to legal analysis, relying upon a morphological understanding of ideology.

Design/methodology/approach

The authors explore ideology within law and legal culture. They examine one such ideology – rule of law – and consider how this can shape judicial decision-making. They suggest techniques by which such influences can be identified.

Findings

The authors make four findings. First, following Freeden, ideology can be understood as a ubiquitous form of political thinking which seeks to fix the meanings of essentially contested concepts. Second, ideology in this sense forms an important part, but is distinguishable from the wider notion of legal culture. Considering ideology in law as a sub-system of legal culture can therefore be fruitful in providing a rich understanding of interpretive disagreements among the judiciary. Third, rule of law as an ideal is itself ideological, as it comprises contested concepts such as certainty, equality, stability and legality. It can be considered to constitute an internal ideology of law and it can be analysed how the concepts are de-contested in individual decisions. Finally, understanding this can help in the analysis of judgments in areas with high levels of administrative discretion and political contestation, such as planning and environmental law, as it helps us to understand how any particular judge sees the role of the court in its wider political context.

Originality/value

The originality of the authors’ approach lies in the drawing together of methodological techniques and understandings of ideology in, and in relation to, law.
Review article: Isolated proximal tibiofibular joint dislocation
Authors: Cunningham Neil J , Farebrother Nicholas , Miles Jake
Published: April 2018

Proximal tibiofibular joint (PTFJ) dislocations are relatively rare injuries and this paper provides an up‐to‐date review and practical management approach for the assessment and management of these cases. Isolated PTFJ dislocations are a rare injury, accounting for less than 1% of all knee injuries. Thus, there does not appear to be a clear consensus on definitive management and post‐reduction care in the literature. This paper provides a review of the literature, anatomical analysis of the PTFJ in the dislocated state, and a technique for reduction. In the majority of cases, PTFJ dislocations are an injury that can be identified with simple imaging modalities and treated in the ED with manipulation under procedural sedation.
A MinION™‐based pipeline for fast and cost‐effective DNA barcoding
Authors: Srivathsan Amrita , Baloğlu Bilgenur , Wang Wendy , Tan Wei X. , Bertrand Denis , Ng Amanda H. Q. , Boey Esther J. H. , Koh Jayce J. Y. , Nagarajan Niranjan , Meier Rudolf
Published: April 2018

DNA barcodes are useful for species discovery and species identification, but obtaining barcodes currently requires a well‐equipped molecular laboratory and is time‐consuming, and/or expensive. We here address these issues by developing a barcoding pipeline for Oxford Nanopore MinION™ and demonstrating that one flow cell can generate barcodes for ~500 specimens despite the high basecall error rates of MinION™ reads. The pipeline overcomes these errors by first summarizing all reads for the same tagged amplicon as a consensus barcode. Consensus barcodes are overall mismatch‐free but retain indel errors that are concentrated in homopolymeric regions. They are addressed with an optional error correction pipeline that is based on conserved amino acid motifs from publicly available barcodes. The effectiveness of this pipeline is documented by analysing reads from three MinION™ runs that represent three different stages of MinION™ development. They generated data for (i) 511 specimens of a mixed Diptera sample, (ii) 575 specimens of ants and (iii) 50 specimens of Chironomidae. The run based on the latest chemistry yielded MinION™ barcodes for 490 of the 511 specimens which were assessed against reference Sanger barcodes (N = 471). Overall, the MinION™ barcodes have an accuracy of 99.3%–100% with the number of ambiguous bases after correction ranging from <0.01% to 1.5% depending on which correction pipeline is used. We demonstrate that it requires ~2 hr of sequencing to gather all information needed for obtaining reliable barcodes for most specimens (>90%). We estimate that up to 1,000 barcodes can be generated in one flow cell and that the cost per barcode can be <USD 2.
Linkage disequilibrium clustering‐based approach for association mapping with tightly linked genomewide data
Authors: Li Zitong , Kemppainen Petri , Rastas Pasi , Merilä Juha
Published: April 2018

Genomewide association studies (GWAS) aim to identify genetic markers strongly associated with quantitative traits by utilizing linkage disequilibrium (LD) between candidate genes and markers. However, because ofLDbetween nearby genetic markers, the standardGWASapproaches typically detect a number of correlatedSNPs covering long genomic regions, making corrections for multiple testing overly conservative. Additionally, the high dimensionality of modernGWASdata poses considerable challenges forGWASprocedures such as permutation tests, which are computationally intensive. We propose a cluster‐basedGWASapproach that first divides the genome into many large nonoverlapping windows and uses linkage disequilibrium network analysis in combination with principal component (PC) analysis as dimensional reduction tools to summarize theSNPdata to independentPCs within clusters of loci connected by highLD. We then introduce single‐ and multilocus models that can efficiently conduct the association tests on such high‐dimensional data. The methods can be adapted to different model structures and used to analyse samples collected from the wild or from biparental F2populations, which are commonly used in ecological genetics mapping studies. We demonstrate the performance of our approaches with two publicly available data sets from a plant (Arabidopsis thaliana) and a fish (Pungitius pungitius), as well as with simulated data.
Climate change and the health of older people in Australia: A scoping review on the role of mobile applications (apps) in ameliorating impact
Authors: Black Deborah A , O'Loughlin Kate , Wilson Leigh A
Published: April 2018

Objectives

Due to the impact of climate change, mobile applications (apps) providing information about the external environment have the potential to improve the health of older people. The purpose of this research was to undertake a scoping review of the evidence on the usability, feasibility and effectiveness of mobile apps to encourage access to activities outside the home in older people.

Methods

A search of databases was undertaken with relevant keywords. Selected manuscripts were judged for relevance to the inclusion criteria and assessed for quality.

Results

Very few published studies examined mobile apps specifically designed to prevent, or to treat, chronic disease in ageing populations, and fewer had rigorous designs. No study addressed accessing the external environment in the context of climate change.

Conclusion

This study demonstrates that there is a gap in the evidence about the mobile apps designed for healthy ageing and, more specifically, to improve access to the external environment.
Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward TLR2 activation
Authors: Iwamoto K. , Nümm T. J. , Koch S. , Herrmann N. , Leib N. , Bieber T.
Published: April 2018

Background

The skin of atopic dermatitis (AD) patients presents a significant dysbalance of the microbiome with a high colonization by Staphylococcus aureus (S. aureus), which positively correlates with the severity of the disease.

Objective

Understanding the role of epidermal dendritic cells (DC) as link between the innate and the adaptive immune systems in AD.

Methods

Comparative phenotypic and functional analysis of TLR2 on Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC) in organotypic models as well as freshly isolated cells from healthy and AD skin.

Results

In situ analysis of freshly isolated LC and IDEC from AD skin revealed decreased TLR2 expression compared to LC from healthy skin. In contrast to IDEC, LC from AD skin failed to display any evidence for in situ activation. Exposure to TLR2 ligand Pam3Cys resulted in maturation and increased migratory activity of LC from normal skin. LC and IDEC from AD were unresponsive to TLR2 ligand in that they failed to mature and displayed a high spontaneous migratory activity. Keratinocytes from both healthy and AD skin expressed similar levels of TLR2. The production of IL‐6 and IL‐10 was impaired by Pam3Cys in supernatants from AD skin. IL‐18 was significantly higher in supernatants from AD skin and not influenced by TLR2 ligation, when compared to healthy skin.

Conclusion

Our results suggest that TLR2‐mediated sensing of S. aureus‐derived signals is strongly impaired in LC from AD skin. This phenomenon may partly contribute to the immune deviation in AD and the lack of S. aureus clearance.
Comparing Types of Financial Incentives to Promote Walking: An Experimental Test
Authors: Burns Rachel J. , Rothman Alexander J.
Published: April 2018

Background

Offering people financial incentives to increase their physical activity is an increasingly prevalent intervention strategy. However, little is known about the relative effectiveness of different types of incentives. This study tested whether incentives based on specified reinforcement types and schedules differentially affected the likelihood of meeting a walking goal and explored if observed behavioural changes may have been attributable to the perceived value of the incentive.

Methods

A 2 (reinforcement type: cash reward, deposit contract) × 2 (schedule: fixed, variable) between‐subjects experiment with a hanging control condition was conducted over 8 weeks (n = 153).

Results

Although walking was greater in the incentive conditions relative to the control condition, walking did not differ across incentive conditions. Exploratory analyses indicated that the perceived value of the incentive was associated with the likelihood of meeting the walking goal, but was not affected by reinforcement type or schedule.

Conclusions

The reinforcement type and schedule manipulations tested in this study did not differentially affect walking. Given that walking behaviour was associated with perceived value, designing incentive strategies that optimise the perceived value of the incentive may be a promising avenue for future research.
Mechanisms of Change in the Relationship between Self‐Compassion, Emotion Regulation, and Mental Health: A Systematic Review
Authors: Inwood Elisa , Ferrari Madeleine
Published: April 2018

Background

Research suggests that self‐compassion may improve mental health by promoting emotion regulation (Berking & Whitley, ). This review aimed to identify studies which investigated the relationship between self‐compassion, emotion regulation, and mental health in order to examine the role of emotional regulation as a mechanism of change.

Methods

Searches were conducted in PsycINFO, CINAHL, Medline complete, Web of Science and Scopus databases. Inclusion criteria required publications to be: peer reviewed, published in English, contain validated measures of self‐compassion and emotion regulation, and report a direct analysis on the relationship between these constructs.

Results

The search yielded five studies which met inclusion criteria. Emotion regulation significantly mediated the relationship between self‐compassion and mental health. This pattern was consistent across community and clinical samples, for a range of mental health symptoms including stress, depression, and post‐traumatic stress disorder. A critical limitation of the review was that all included studies used cross‐sectional data, limiting interpretations regarding causation.

Conclusions

Results provide preliminary evidence that emotion regulation may be a mechanism of change in the relationship between self‐compassion and mental health. Self‐compassion may be a pertinent preliminary treatment target for individuals who avoid experiences of emotions.
Sucrose assists selection of high‐quality oocytes in pigs
Authors: Dang‐Nguyen Thanh Quang , Nguyen Hiep Thi , Somfai Tamas , Wells David , Men Nguyen Thi , Viet‐Linh Nguyen , Noguchi Junko , Kaneko Hiroyuki , Kikuchi Kazuhiro , Nagai Takashi
Published: April 2018

We investigated whether high‐quality in vitro matured (IVM) oocytes can be distinguished from poor ones based on the morphological changes after treatment with hyperosmotic medium containing 0.2 mol/L sucrose in pigs. We hypothesize that IVM oocytes maintaining round shape have higher quality than mis‐shapened oocytes following dehydration. Oocyte quality was verified by determining embryonic developmental competence using in vitro fertilization, nuclear transfer and parthenogenetic activation. In all cases, the round oocytes had greater (p < .05) developmental competence than that of mis‐shapened oocytes in terms of blastocyst rate and total cell number in blastocysts obtained after 6 days of in vitro culture. We also confirm that round aged oocytes are higher in quality than mis‐shapened aged oocytes. In an attempt to find out why high‐quality oocytes maintain a round shape whereas poorer oocytes become mis‐shapened following sucrose treatment, we examined the arrangement of actin microfilaments and microtubules. Abnormal organization of these cytoskeletal components was higher (p < .05) in mis‐shapened oocytes compared to round oocytes after 52 hr of IVM. In conclusion, sucrose treatment helps selection of high‐quality oocytes, including aged oocytes, in pigs. Abnormal cytoskeleton arrangements partly explain for low developmental competence of mis‐shapened oocytes.
Identification of novel diagnostic biomarkers for deep venous thrombosis
Authors: Memon Ashfaque A. , Sundquist Kristina , PirouziFard Mirnabi , Elf Johan L. , Strandberg Karin , Svensson Peter J. , Sundquist Jan , Zöller Bengt
Published: April 2018

The combination of a negative D‐dimer and a Wells score can rule out, but not confirm, a diagnosis of deep venous thrombosis (DVT). We aimed to identify new diagnostic biomarkers for DVT and to investigate their relationship with hypercoagulability markers [D‐dimer and activated protein C‐protein C inhibitor (APC‐PCI) complex]. We screened 92 cardiovascular‐specific proteins in plasma samples from 45 confirmed DVT patients and 45 age‐ and sex‐matched non‐DVT patients selected from a prospective multicentre diagnostic management study (SCORE) by Proseek Multiplex CVDIII96×96. Plasma levels of 30 proteins were significantly different between DVT and non‐DVT patients. After Bonferroni correction, plasma levels of seven proteins: P‐selectin, transferrin receptor protein 1, von Willebrand factor, tissue factor pathway inhibitor, osteopontin (OPN), bleomycin hydrolase and ST2 protein remained significantly different. The area under curve (AUC) for these proteins ranged from 0·70 to 0·84. Furthermore, all seven identified proteins were significantly associated with markers of hypercoagulability. A combination of OPN and APC‐PCI had the best ability to discriminate DVT from non‐DVT patients (AUC = 0·94; sensitivity = 89% and specificity = s84%). In conclusion, we identified multiple proteins associated with markers of hypercoagulability and with a potential to become novel diagnostic biomarkers for DVT.
Contemporary outcomes of hypospadias retrieval surgery in adults
Authors: Aldamanhori Reem B. , Osman Nadir I. , Inman Richard D. , Chapple Christopher R.
Published: April 2018

Objective

To describe the surgical approach and outcomes in the treatment of adult patients with complications of childhood hypospadias surgery, as such patients present a significant reconstructive challenge due to the combination of anatomical and cosmetic deformity, which often results in major functional and psychosexual sequelae.

Patients and Methods

We analysed prospectively collected data on 79 adults with complications of childhood hypospadias surgery, who were operated on between 2004 and 2016. Of the 79 patients, 48 underwent a two‐stage urethroplasty using a buccal mucosa graft, and 31 underwent a one‐stage distal urethroplasty.

Results

Patients were followed up using flexible cystoscopy (every 6–9 months). The mean (range) follow‐up was 48 (12–96) months. Of the 48 patients who underwent a two‐stage repair, eight (16%) needed a revision of the first‐stage graft. In total, nine of the 48 patients (16%) developed fistula requiring closure after the second stage; all but one was closed successfully on the first attempt, whilst one required two attempts before closure. Only two of the 48 patients that underwent a two‐stage procedure required a re‐do urethroplasty within 3 years. Of the 31 patients who underwent a one‐stage repair, six (19%) needed fistula closure, all of which were successful. No patient required a further urethroplasty during follow‐up.

Conclusions

Despite the significant surgical challenges found in this patient group, excellent long‐term functional outcomes can be achieved. As expected there is a need for additional intervention, either for revision of the first stage or to close fistulae and less commonly for further reconstruction for stricture recurrence.
Epithelial‐to‐mesenchymal transition in the context of epidermal growth factor receptor inhibition in non‐small‐cell lung cancer
Authors: Bronte Giuseppe , Bravaccini Sara , Bronte Enrico , Burgio Marco Angelo , Rolfo Christian , Delmonte Angelo , Crinò Lucio
Published: April 2018

The identification of oncogenic driver mutations in non‐small‐cell lung cancer (NSCLC) has led to the development of targeted drugs. Tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) target lung tumours bearing EGFR‐activating mutations. This new therapeutic strategy has greatly improved tumour response rates. However, drug resistance invariably occurs during TKI‐based treatment. Epithelial‐to‐mesenchymal transition (EMT) is one of the resistance mechanisms identified in EGFR‐mutated NSCLC treated with TKIs. In this review we gather together the most important findings on this phenomenon in relation to cancer stem cells and cancer epigenetics. We also outline the correlation between the effects of stromal factors from the microenvironment, the transcription factors activated, the epigenetic changes in chromatin, and the evolution of cellular behaviour. Notably, EMT has already been shown to be the link between benign lung diseases such as chronic obstructive pulmonary disease and lung carcinogenesis. The various mechanisms of acquired resistance to EGFR‐TKIs are also briefly described to provide background information on EMT. Our extensive review of the scientific literature serves to highlight the cellular and molecular events that lead to the onset of EMT in NSCLC cells treated with EGFR‐TKIs. Finally, we put forward a hypothesis to explain why, in some cases, EMT rather than other known mechanisms is involved in resistance to TKIs.
Young age is associated with increased rates of residual and recurrent paediatric differentiated thyroid carcinoma
Authors: Hampson Sarah , Stephens Derek , Wasserman Jonathan D.
Published: April 2018

Objective

Differentiated thyroid carcinoma is rare in young children. There are conflicting data as to whether disease in this age group differs from that in adolescents and specifically, if it is more aggressive. Current practice guidelines do not differentiate treatment between these groups, but speculate that differences may exist. We sought to compare clinical features, treatment and outcomes between children (<12 years) and adolescents (12‐18 years) with thyroid nodules and thyroid malignancy over a 20‐year period.

Design

Retrospective case series at a single tertiary care hospital.

Patients

A total of 177 children 0‐18 years of age at the time of diagnosis of a thyroid nodule and/or malignancy between 1992 and 2012.

Results

There was a significantly higher female‐to‐male ratio in patients 12‐18 years with benign and malignant nodules compared to those under 12. There was no difference across age groups with respect to cytology or histology, size, surgical approach or nodal status. Younger patients had a higher lymph node ratio. Younger patients received a higher cumulative dose of radioactive iodine (97.6 mCi/m2) vs older patients (75.9 mCi/m2) and had higher rates of pulmonary metastatic disease, although the differences did not achieve significance. Finally, children were less likely than adolescents to achieve a state of undetectable disease and fewer of the younger children remained disease‐free.

Conclusions

Despite comparable apparent initial disease burden and treatment, younger children have poorer outcomes when compared to adolescents, even in the absence of nodal metastases and thus may warrant intensification of primary therapy and/or tumour surveillance.