bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer
Authors: Lebrero‐Fernández Cristina , Wenzel Ulf Alexander , Akeus Paulina , Wang Ying , Strid Hans , Simrén Magnus , Gustavsson Bengt , Börjesson Lars G. , Cardell Susanna L. , Öhman Lena , Quiding‐Järbrink Marianne , Bas‐Forsberg Anna
Published: April 2016

Several Butyrophilin (BTN) and Btn‐like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real‐time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2−/−) and intestinal tumorigenesis (ApcMin/+). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially BTN1A1, BTN2A2, BTN3A3, and BTNL8 were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of BTNL2, BTNL3, BTNL8, and BTNL9 as compared to unaffected tissue. Colonic inflammation in Muc2−/− mice significantly down‐regulated the expression of particularly Btnl1, Btnl4, and Btnl6 mRNA, and intestinal polyps derived from ApcMin/+ mice displayed altered levels of Btn1a1, Btn2a2, and Btnl1 transcripts. Thus, our data present an association of BTN and BTNL genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.
Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate
Authors: Hanyuda Akiko , Ogino Shuji , Qian Zhi Rong , Nishihara Reiko , Song Mingyang , Mima Kosuke , Inamura Kentaro , Masugi Yohei , Wu Kana , Meyerhardt Jeffrey A. , Chan Andrew T. , Fuchs Charles S. , Giovannucci Edward L. , Cao Yin
Published: April 2016

Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980‐2010) and the Health Professionals Follow‐up Study (1986‐2010). Utilizing duplication‐method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's‐like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor‐infiltrating lymphocytes, the overall lymphocytic reaction score, or T‐cell [CD3+, CD8+, CD45RO (PTPRC)+ or FOXP3+] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person‐years), we documented 1,436 incident rectal and colon cancer cases with available formalin‐fixed paraffin‐embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T‐cell infiltration in tumor tissue status (Pheterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.
Interceptor Drainage Modelling to Manage High Groundwater Table on the Abyek Plain, Iran
Authors: Ghorbani Karim , Lee Teang Shui , Wayayok Aimrun , Boroomand Nasab Saeed
Published: April 2016

High groundwater tables and soil salinity are a serious threat to agricultural areas, especially on the Abyek Plain, Iran. An interceptor drainage system was installed to lower the groundwater head and control soil salinity. Simulation is an appropriate approach to investigate possible groundwater behaviour in future conditions and to explore suitable designs for implementation. Ninety‐nine observation wells were installed around the interceptor drainage system in the Abyek Plain to monitor groundwater movement and salinity changes. Groundwater table fluctuation was measured monthly for 3 years from December 2010 until January 2014. A MODFLOW model was calibrated for the study area using the data measured through the observation wells. Assessment of the measured values indicated that the groundwater head was lowered within the 3 years due to the installation of the system. A calibrated model was applied to predict the future conditions of groundwater levels and suggest proper designs. Groundwater level drawdowns were predicted at approximately 1.3 and 1.5 m for August 2018 and August 2025, respectively. The results also revealed that with the installation of additional parallel interceptor drainage at a distance of 1000 m from the existing drainage, the groundwater table could be lowered in a large area of the plain. Copyright © 2016 John Wiley & Sons, Ltd.
Endothelial cell dysfunction in globoid cell leukodystrophy
Authors: Belleri Mirella , Presta Marco
Published: April 2016

Angiogenesis plays a pivotal role in the physiology and pathology of the brain. Microvascular alterations have been observed in various neurodegenerative disorders, including genetic leukodystrophies. Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by β‐galactosylceramidase (GALC) deficiency and characterized by the accumulation of the neurotoxic metabolite psychosine in the central nervous system and peripheral tissues. Structural and functional alterations occur in the microvascular endothelium of the brain of GLD patients and twitcher mice, a murine model of the disease. In addition, increased vessel permeability and a reduced capacity to respond to proangiogenic stimuli characterize the endothelium of twitcher animals. On the one hand, these alterations may depend, at least in part, on the local and systemic angiostatic activity exerted by psychosine on endothelial cells. On the other hand, studies performed in vivo on zebrafish embryos and in vitro on human endothelial cells suggest that GALC downregulation may also lead to psychosine‐independent neuronal and vascular defects. Together, experimental observations indicate that endothelial cell dysfunctions may represent a novel pathogenic mechanism in human leukodystrophies, including GLD. A better understanding of the molecular mechanisms responsible for these microvascular alterations may provide new insights for the therapy of GLD. © 2016 Wiley Periodicals, Inc.
Instrumentality, Expressivity, and Relational Qualities in the Same‐Sex Friendships of College Women and Men
Authors: Frey Lisa L. , Beesley Denise , Hurst Rebecca , Saldana Star , Licuanan Brian
Published: April 2016

Using the relational–cultural model (Jordan, Kaplan, Miller, Stiver, & Surrey, 1991), the authors hypothesized that instrumentality, expressivity, and the individual affective experience of same‐sex friendships would predict increased relationship mutuality, with college women and men showing different predictive patterns. Overall, results supported the hypotheses. Gender moderated the associations among variables, notably between mutuality and individual affective experiences of same‐sex friendships. Implications for counselors serving college student populations are discussed.
Eating Disorders: Explanatory Variables in Caucasian and Hispanic College Women
Authors: Aviña Vanessa , Day Susan X
Published: April 2016

The authors explored Hispanic and Caucasian college women's (N = 264) behavioral and attitudinal symptoms of eating disorders after controlling for body mass index and internalization of the thinness ideal, as well as the roles of ethnicity and ethnic identity in symptomatology. Correlational analysis, multivariate analysis of variance, and regression analysis suggested more similarities than differences between Hispanic and Caucasian college women in terms of eating disorders.
A surface plasmon resonance system for the underwater detection of domoic acid
Authors: Colas Florent , Crassous Marie‐Pierre , Laurent Sebastien , Litaker Richard W. , Rinnert Emmanuel , Le Gall Erwan , Lunven Michel , Delauney Laurent , Compère Chantal
Published: April 2016

Over the past decade Surface Plasmon Resonance (SPR) techniques have been applied to the measurement of numerous analytes. In this article, an SPR biosensor system deployed from an oceanographic vessel was used to measure dissolved domoic acid (DA), a common and harmful phycotoxin produced by certain microalgae species belonging to the genus Pseudo‐nitzschia. During the biosensor deployment, concentrations of Pseudo‐nitzschia cells were very low over the study area and measured DA concentrations were below detection. However, the in situ operational detection limit of the system was established using calibrated seawater solutions spiked with DA. The system could detect the toxin at concentrations as low as 0.1 ng mL−1 and presented a linear dynamic range from 0.1 ng mL−1 to 2.0 ng mL−1. This sensor showed promise for in situ detection of DA.
Pseudodifferential operators on mixed‐norm Besov and Triebel–Lizorkin spaces
Authors: Georgiadis A. G. , Nielsen M.
Published: April 2016

We prove boundedness of pseudodifferential operators on anisotropic mixed‐norm Besov and Triebel–Lizorkin spaces. Our proof relies only on general maximal function estimates and provides a new perspective even in the case of spaces without mixed norms. Moreover, we cover the case of Fourier multipliers on the above mentioned spaces. As application we establish boundedness of pseudodifferential operators and Fourier multipliers on anisotropic mixed‐norm Sobolev spaces.
Hexagonal gradient scheme with RF spoiling improves spoiling performance for high‐flip‐angle fast gradient echo imaging
Authors: Hess Aaron T. , Robson Matthew D.
Published: April 2016

Purpose

To present a framework in which time‐varying gradients are applied with RF spoiling to reduce unwanted signal, particularly at high flip angles.

Methods

A time‐varying gradient spoiler scheme compatible with RF spoiling is defined, in which spoiler gradients cycle through the vertices of a hexagon, which we call hexagonal spoiling. The method is compared with a traditional constant spoiling gradient both in the transition to and in the steady state. Extended phase graph (EPG) simulations, phantom acquisitions, and in vivo images were used to assess the method.

Results

Simulations, phantom and in vivo experiments showed that unwanted signal was markedly reduced by employing hexagonal spoiling, both in the transition to and in the steady state. For adipose tissue at 1.5 Tesla, the unwanted signal in the steady state with a 60 ° flip angle was reduced from 22% with constant spoiling to 2% with hexagonal spoiling.

Conclusions

A time‐varying gradient spoiler scheme that works with RF spoiling, called “hexagonal spoiling,” has been presented and found to offer improved spoiling over the traditional constant spoiling gradient. Magn Reson Med 77:1231–1237, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Pelvic floor muscle function, pelvic floor dysfunction and diastasis recti abdominis: Prospective cohort study
Authors: Bø Kari , Hilde Gunvor , Tennfjord Merete Kolberg , Sperstad Jorun Bakken , Engh Marie Ellstrøm
Published: April 2016

Aims

Compare vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength, and endurance in women with and without diastasis recti abdominis at gestational week 21 and at 6 weeks, 6 months, and 12 months postpartum. Furthermore, to compare prevalence of urinary incontinence (UI) and pelvic organ prolapse (POP) in the two groups at the same assessment points.

Methods

This is a prospective cohort study following 300 nulliparous pregnant women giving birth at a public university hospital. VRP, PFM strength, and endurance were measured with vaginal manometry. ICIQ‐UI‐SF questionnaire and POP‐Q were used to assess UI and POP. Diastasis recti abdominis was diagnosed with palpation of  ≥2 fingerbreadths 4.5 cm above, at, or 4.5 cm below the umbilicus.

Results

At gestational week 21 women with diastasis recti abdominis had statistically significant greater VRP (mean difference 3.06 cm H2O [95%CI: 0.70; 5.42]), PFM strength (mean difference 5.09 cm H2O [95%CI: 0.76; 9.42]) and PFM muscle endurance (mean difference 47.08 cm H2O sec [95%CI: 15.18; 78.99]) than women with no diastasis. There were no statistically significant differences between women with and without diastasis in any PFM variables at 6 weeks, 6 months, and 12 months postpartum. No significant difference was found in prevalence of UI in women with and without diastasis at any assessment points. Six weeks postpartum 15.9% of women without diastasis had POP versus 4.1% in the group with diastasis (P = 0.001).

Conclusions

Women with diastasis were not more likely to have weaker PFM or more UI or POP. Neurourol. Urodynam. 36:716–721, 2017. © 2016 Wiley Periodicals, Inc.
Benchmarking sustainability performance: the next step in building sustainable business models
Authors: Maltz Elliot , Bi Henry H. , Bateman Mark
Published: April 2016

Developing sustainable business models incorporating effects on people, profit, and planet is becoming an increasingly important strategic issue. Benchmarking with peer companies can assist a company in setting goals of improving its performance. As such, developing a methodology for effectively benchmarking sustainable business practices is an important step in the evolution of sustainability management. However, a company's sustainability performance is composed of many elements that may involve difficult tradeoffs, and its performance may vary over time. In this paper, we propose a data‐driven approach of innovatively adapting statistical process control charts, conventionally used in quality control, to simultaneously compare multiple performance measures and analyze variation in both trend and performance among companies in a given industry. We apply this approach to benchmarking the sustainability performance of companies in the US utility industry and demonstrate it is robust and reliable for benchmarking the performance of companies in virtually all industries. Copyright © 2016 John Wiley & Sons, Ltd.
The IMI PROTECT project: purpose, organizational structure, and procedures
Authors: Reynolds Robert F. , Kurz Xavier , de Groot Mark C.H. , Schlienger Raymond G. , Grimaldi‐Bensouda Lamiae , Tcherny‐Lessenot Stephanie , Klungel Olaf H.
Published: April 2016

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty‐five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug–adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug–adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally. Copyright © 2016 John Wiley & Sons, Ltd.
Disordered nucleiome: Abundance of intrinsic disorder in the DNA‐ and RNA‐binding proteins in 1121 species from Eukaryota, Bacteria and Archaea
Authors: Wang Chen , Uversky Vladimir N. , Kurgan Lukasz
Published: April 2016

Intrinsically disordered proteins (IDPs) are abundant in various proteomes, where they play numerous important roles and complement biological activities of ordered proteins. Among functions assigned to IDPs are interactions with nucleic acids. However, often, such assignments are made based on the guilty‐by‐association principle. The validity of the extension of these correlations to all nucleic acid binding proteins has never been analyzed on a large scale across all domains of life. To fill this gap, we perform a comprehensive computational analysis of the abundance of intrinsic disorder and intrinsically disordered domains in nucleiomes (∼548 000 nucleic acid binding proteins) of 1121 species from Archaea, Bacteria and Eukaryota. Nucleiome is a whole complement of proteins involved in interactions with nucleic acids. We show that relative to other proteins in the corresponding proteomes, the DNA‐binding proteins have significantly increased disorder content and are significantly enriched in disordered domains in Eukaryotes but not in Archaea and Bacteria. The RNA‐binding proteins are significantly enriched in the disordered domains in Bacteria, Archaea and Eukaryota, while the overall abundance of disorder in these proteins is significantly increased in Bacteria, Archaea, animals and fungi. The high abundance of disorder in nucleiomes supports the notion that the nucleic acid binding proteins often require intrinsic disorder for their functions and regulation.
Negative Poisson's ratio in cubic materials along principal directions
Authors: Ho Duc Tam , Park Soon‐Dong , Kwon Soon‐Yong , Han Tong‐Seok , Kim Sung Youb
Published: April 2016

This report employed molecular statics simulation and density‐functional‐theory calculation to study the Poisson's ratios of face‐centered‐cubic materials. We provide numerical and theoretical evidences to show that cubic materials can exhibit auxetic behavior in a principal direction under proper loading conditions. When a stress perpendicular to the loading direction is applied, cubic materials can exhibit a negative Poisson's ratio at finite strain. The negative Poisson's ratio behavior, including its direction and value, is highly dependent on the direction and magnitude of the transversely applied stresses. As a result, we show that it is possible to tune the direction and magnitude of the negative Poisson's ratio behavior of cubic materials by controlling the transverse loadings.
Right‐side pulmonary agenesis with atrial septal defect in adult
Authors: Das Shukla Amitabh , Agrawal Neha , Chandra Alok , Anantha Shreenivasa , Chaudhary Abhinav
Published: April 2016

Pulmonary agenesis, a rare congenital condition, is incompatible with life when present bilateral, while unilateral agenesis is usually detected in infancy or early childhood. Rare asymptomatic patients may reach adulthood undiagnosed, with signs mimicking common conditions presenting as radiopaque hemithorax with ipsilateral mediastinal shift. Here, we describe a case of a young lady, with history of consanguinity, who presented with complaints, suggestive of lower respiratory tract infection, and was investigated and diagnosed to be a case of right‐side pulmonary agenesis with large ostium secondum atrial septal defect. Our present case emphasizes the importance of presence of pulmonary agenesis with cardiac congenital anomaly, remaining asymptomatic until adulthood, particularly in patients born of parents with consanguineous marriages.
Evaluating Methods to Establish Habitat Suitability Criteria: A Case Study in the Upper Delaware River Basin, USA
Authors: Galbraith H. S. , Blakeslee C. J. , Cole J. C. , Talbert C. A. , Maloney K. O.
Published: April 2016

Defining habitat suitability criteria (HSC) of aquatic biota can be a key component to environmental flow science. HSC can be developed through numerous methods; however, few studies have evaluated the consistency of HSC developed by different methodologies. We directly compared HSC for depth and velocity developed by the Delphi method (expert opinion) and by two primary literature meta‐analyses (literature‐derived range and interquartile range) to assess whether these independent methods produce analogous criteria for multiple species (rainbow trout, brown trout, American shad, and shallow fast guild) and life stages. We further evaluated how these two independently developed HSC affect calculations of habitat availability under three alternative reservoir management scenarios in the upper Delaware River at a mesohabitat (main channel, stream margins, and flood plain), reach, and basin scale. In general, literature‐derived HSC fell within the range of the Delphi HSC, with highest congruence for velocity habitat. Habitat area predicted using the Delphi HSC fell between the habitat area predicted using two literature‐derived HSC, both at the basin and the site scale. Predicted habitat increased in shallow regions (stream margins and flood plain) using literature‐derived HSC while Delphi‐derived HSC predicted increased channel habitat. HSC generally favoured the same reservoir management scenario; however, no favoured reservoir management scenario was the most common outcome when applying the literature range HSC. The differences found in this study lend insight into how different methodologies can shape HSC and their consequences for predicted habitat and water management decisions. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Clay‐filled starch films. Part I: Effect of clay kind and glycerol concentration on functional properties of composites
Authors: Staroszczyk Hanna , Gottfried Karolina , Malinowska‐Pańczyk Edyta , Kołodziejska Ilona
Published: April 2016

The aim of this work was to improve the mechanical and water barrier properties of composite films prepared from starch and clays, plasticized with glycerol at different concentrations. The effects of hydrophilic Closite Na+ and Nanomer PGV were compared with that exerted by organically modified more hydrophobic Nanofil 2 and NanoBent ZR‐1. The antimicrobial activity of composites containing hydrophobic clays was also investigated. The hydrophilic Nanomer PGV at concentrations of 5–10% increased the tensile strength (TS) of unplasticized composites, but starch‐Closite Na+ composites were too brittle to measure their mechanical properties. The hydrophobic clays did not improve the mechanical properties of the unplasticized composites. In the presence of glycerol at concentrations of 20–30%, TS of composites containing hydrophilic clays and even hydrophobic NanoBent ZR‐1 increased in comparison to plasticized films without clay. None of the clays improved the water barrier properties of the unplasticized composites, while in the plasticized composites all the clays decreased the water vapor permeability to an extent dependent on the kind and concentration of clay and glycerol concentration. Starch‐NanoBentZR‐1 composite showed very high activity against gram‐positive Staphylococcus aureus and Listeria innocua. Starch‐Nanofil 2 composites were characterized by smaller activity. Neither composite showed any antimicrobial activity, or their activity against gram‐negative bacteria was low.
Synthesis and Physico‐Chemical Properties of Sodium 3‐Oxo‐2‐(3‐(4‐sulphonatophenyl)triaz‐2‐enyl)octadecanoate Anionic Surfactant
Authors: El‐Sharkawy El‐Sayed A. , Mead Attia I. , Abdel Reheim Mohamed A. M. , Tolba Ahmed M.
Published: April 2016

The novel anionic surfactant sodium 3‐oxo‐2‐(3‐(4‐sulphonatophenyl)triaz‐2‐enyl)octadecanoate (SSTO) was prepared from renewable raw materials; glycine and palmitic acid. Surface and bulk properties of SSTO were investigated by surface tension and electrical conductivity techniques at 298, 308, 318 and 328 K. Surface properties including critical micelle concentration (CMC), maximum surface excess concentration (Γmax), minimum area per molecule (Amin), surface tension at CMC (γCMC), effectiveness of surface tension reduction (ΠCMC), efficiency of surface adsorption (pC20), and degree of counterion dissociation (α) were determined. The thermodynamic parameters of micellization (ΔG°mic, ΔH°mic and ΔS°mic) and adsorption (ΔG°ad, ΔH°ad and ΔS°ad) were also investigated at 298, 308, 318 and 328 K. The effect of 3 wt% n‐propanol, n‐butanol and n‐pentanol on surface tension and conductivity at 298 K was also determined.
Pathoconnectomics of cognitive impairment in small vessel disease: A systematic review
Authors: Dey Ayan K. , Stamenova Vessela , Turner Gary , Black Sandra E. , Levine Brian
Published: April 2016

Introduction

Cerebral small vessel disease (CSVD) is a highly prevalent condition associated with diffuse ischemic damage and cognitive dysfunction particularly in executive function and attention. Functional brain imaging studies can reveal mechanisms of cognitive impairment in CSVD, although findings are mixed.

Methods

A systematic review integrating findings from functional magnetic resonance imaging and electroencephalography in CSVD is involved.

Results

CSVD damages long‐range white matter tracts connecting nodes within distributed brain networks. It also disrupts frontosubcortical circuits and cholinergic fiber tracts mediating attentional processes. These changes, illustrated within a model of network dynamics, synergistically relate to neurodegenerative pathology contributing to dementia.

Discussion

The effects of CSVD on attention and executive functioning are best understood within a network model of cognition as revealed by functional neuroimaging. Analysis of network function in CSVD can improve characterization of disease severity and treatment effects, and it can inform theoretical models of brain function.
2dSpAn: semiautomated 2-d segmentation, classification and analysis of hippocampal dendritic spine plasticity
Authors: Basu Subhadip , Plewczynski Dariusz , Saha Satadal , Roszkowska Matylda , Magnowska Marta , Baczynska Ewa , Wlodarczyk Jakub
Published: April 2016

Motivation: Accurate and effective dendritic spine segmentation from the dendrites remains as a challenge for current neuroimaging research community. In this article, we present a new method (2dSpAn) for 2-d segmentation, classification and analysis of structural/plastic changes of hippocampal dendritic spines. A user interactive segmentation method with convolution kernels is designed to segment the spines from the dendrites. Formal morphological definitions are presented to describe key attributes related to the shape of segmented spines. Spines are automatically classified into one of four classes: Stubby, Filopodia, Mushroom and Spine-head Protrusions.

Results: The developed method is validated using confocal light microscopy images of dendritic spines from dissociated hippocampal cultures for: (i) quantitative analysis of spine morphological changes, (ii) reproducibility analysis for assessment of user-independence of the developed software and (iii) accuracy analysis with respect to the manually labeled ground truth images, and also with respect to the available state of the art. The developed method is monitored and used to precisely describe the morphology of individual spines in real-time experiments, i.e. consequent images of the same dendritic fragment.

Availability and Implementation: The software and the source code are available at https://sites.google.com/site/2dspan/ under open-source license for non-commercial use.

Contact:  subhadip@cse.jdvu.ac.in or j.wlodarczyk@nencki.gov.pl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inferring heterozygosity from ancient and low coverage genomes
Authors: Kousathanas Athanasios , Leuenberger Christoph , Link Vivian , Sell Christian , Burger Joachim , Wegmann Daniel
Published: April 2016

While genetic diversity can be quantified accurately from high coverage sequencing, it is often desirable to obtain such estimates from low coverage data, either to save costs or because of low DNA quality as observed for ancient samples. Here we introduce a method to accurately infer heterozygosity probabilistically from very low coverage sequences of a single individual. The method relaxes the infinite sites assumption of previous methods, does not require a reference sequence and takes into account both variable sequencing errors and potential post-mortem damage. It is thus also applicable to non-model organisms and ancient genomes. Since error rates as reported by sequencing machines are generally distorted and require recalibration, we also introduce a method to infer accurately recalibration parameter in the presence of post-mortem damage. This method does also not require knowledge about the underlying genome sequence, but instead works from haploid data (e.g. from the X-chromosome from mammalian males) and integrates over the unknown genotypes. Using extensive simulations we show that a few Mb of haploid data is sufficient for accurate recalibration even at average coverages as low as 1-3x. At similar coverages, out method also produces very accurate estimates of heterozygosity down to 10−4within windows of about 1Mb. We further illustrate the usefulness of our approach by inferring genome-wide patterns of diversity for several ancient human samples and found that 3,000-5,000 samples showed diversity patterns comparable to modern humans. In contrast, two European hunter-gatherer samples exhibited not only considerably lower levels of diversity than modern samples, but also highly distinct distributions of diversity along their genomes. Interestingly, these distributions were also very differently between the two samples, supporting earlier conclusions of a highly diverse and structured population in Europe prior to the arrival of farming.
Anthropology education and public engagement: Where do we go from here?
Authors: Basu Paul
Published: April 2016

This guest editorial considers educational initiatives in the field of anthropology, with a particular focus on what has been learnt from the RAI experiences in setting up the now aborted A‐level.
Exceptional educators: a collaborative training partnership for the inclusion of students with Down's syndrome
Authors: Vaughan Michelle , Henderson Anne
Published: April 2016

This article discusses the results of a teacher training initiative in the United States. Exceptional Educators is the result of an inter‐organisational collaboration between a community‐based organisation (Gold Coast Down Syndrome Organization), the local public school system and a university professor. The training focuses on three distinct objectives; understanding the physical and emotional needs of the disability, creating modified curriculum units based on individual learning goals and recognising common behavioral problems that arise in school settings. Overall, the results showed positive outcomes, with gains in knowledge of curriculum modification, behavioural strategies and overall understanding of Down's syndrome, as well as an increase in confidence level. A six‐week follow‐up survey indicated that the majority of the participants used the information presented back in their teaching environments. This study also investigated the added value of this collaboration, finding that the community connection often continues past the training and has provided teachers additional avenues for support.
Atheroprotective effects of conjugated linoleic acid
Authors: Bruen Robyn , Fitzsimons Stephen , Belton Orina
Published: April 2016

Atherosclerosis, the underlying cause of heart attack and strokes, is a progressive dyslipidaemic and inflammatory disease where monocyte‐derived macrophage cells play a pivotal role. Although most of the mechanisms that contribute to the progression of atherosclerosis have been identified, there is limited information on those governing regression. Conjugated linoleic acid (CLA) is a generic term denoting a group of naturally occurring isomers of linoleic acid (18:2, n6) that differ in the position or geometry (i.e. cis or trans) of their double bonds. The most predominant isomers in ruminant fats are cis‐9, trans‐11 CLA (c9,t11‐CLA), which accounts for more than 80% of CLA isomers in dairy products and trans‐10, cis‐12 CLA (t10,c12‐CLA). Dietary administration of a blend of the two most abundant isomers of CLA has been shown to inhibit the progression and induce the regression of pre‐established atherosclerosis. Studies investigating the mechanisms involved in CLA‐induced atheroprotective effects are continually emerging. The purpose of this review is to discuss comprehensively the effects of CLA on monocyte/macrophage function in atherosclerosis and to identify possible mechanisms through which CLA mediates its atheroprotective effects.
Developing consensus on hospital prescribing indicators of potential harm for infants and children
Authors: Fox Andy , Pontefract Sarah , Brown David , Portlock Jane , Coleman Jamie
Published: April 2016

Aims

The aim of the study was to develop a list of hospital based paediatric prescribing indicators that can be used to assess the impact of electronic prescribing or clinical decision support tools on paediatric prescribing errors.

Methods

Two rounds of an electronic consensus method (eDelphi) were carried out with 21 expert panellists from the UK. Panellists were asked to score each prescribing indicator for its likelihood of occurrence and severity of outcome should the error occur. The scores were combined to produce a risk score and a median score for each indicator calculated. The degree of consensus between panellists was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or higher was achieved and were in the high risk categories.

Results

Each of the 21 panellists completed an exploratory round and two rounds of scoring. This identified 41 paediatric prescribing indicators with a high risk rating and greater than 80% consensus. The most common error type within the indicators was wrong dose (n = 19) and the most common drug classes were antimicrobials (n = 10) and cardiovascular (n = 7).

Conclusions

A set of 41 paediatric prescribing indicators describing potential harm for the hospital setting has been identified by an expert panel. The indicators provide a standardized method of evaluation of prescribing data on both paper and electronic systems. They can also be used to assess implementation of clinical decision support systems or other quality improvement initiatives.
Bisphenol A Increases the Migration and Invasion of Triple‐Negative Breast Cancer Cells via Oestrogen‐related Receptor Gamma
Authors: Zhang Xiao‐Lin , Liu Na , Weng Shan‐Fan , Wang Hong‐Sheng
Published: April 2016

Triple‐negative breast cancer (TNBC) is characterized by great metastasis and invasion capability. Our study revealed that nanomolar bisphenol A (BPA), one of the most ubiquitous endocrine disruptors, can increase wound closure and invasion of both MDA‐MB‐231 and BT‐549 cells. BPA treatment can increase protein and mRNA expression of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9, while had no effect on the expression of vimentin (Vim) and fibronectin (FN) in TNBC cells. The expression of G‐protein‐coupled receptor (GPER), which has been suggested to mediate rapid oestrogenic signals, was not varied in BPA‐treated MDA‐MB‐231 and BT‐549 cells. Its inhibitor G15 also had no effect on BPA‐induced MMPs expression and cell invasion. Interestingly, BPA treatment can significantly increase the mRNA and protein expressions of oestrogen‐related receptor γ (ERRγ), but not ERRα or ERRβ, in both MDA‐MB‐231 and BT‐549 cells. The knock‐down of ERRγ can markedly attenuate BPA‐induced expression of MMP‐2 and MMP‐9 in TNBC cells. BPA treatment can activate both ERK1/2 and Akt in TNBC cells. Both inhibitors of ERK1/2 (PD98059) and Akt (LY294002) can attenuate BPA‐induced ERRγ expression and cell invasion of MDA‐MB‐231 cells. Collectively, our data revealed that BPA can increase the expression of MMPs and in vitro motility of TNBC cells via ERRγ. Both activation of ERK1/2 and Akt participated in this process. Our study suggests that more attention should be paid to the roles of xenoestrogens such as BPA in the development and progression of TNBC.
Comparing Biomarkers as Trial Level General Surrogates
Authors: Gabriel Erin E. , Daniels Michael J. , Halloran M. Elizabeth
Published: April 2016

An intermediate response measure that accurately predicts efficacy in a new setting can reduce trial cost and time to product licensure. In this article, we define a trial level general surrogate, which is an intermediate response that can be used to accurately predict efficacy in a new setting. Methods for evaluating general surrogates have been developed previously. Many methods in the literature use trial level intermediate responses for prediction. However, all existing methods focus on surrogate evaluation and prediction in new settings, rather than comparison of candidate general surrogates, and few formalize the use of cross validation to quantify the expected prediction error. Our proposed method uses Bayesian non-parametric modeling and cross-validation to estimate the absolute prediction error for use in evaluating and comparing candidate trial level general surrogates. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate trial level general surrogates in several multi-national trials of a pentavalent rotavirus vaccine. We identify at least one immune measure that has potential value as a trial level general surrogate and use it to predict efficacy in a new trial where the clinical outcome was not measured.
Novel Piperine Derivatives with Antidiabetic Effect as PPAR‐γ Agonists
Authors: Kharbanda Chetna , Alam Mohammad Sarwar , Hamid Hinna , Javed Kalim , Bano Sameena , Ali Yakub , Dhulap Abhijeet , Alam Perwez , Pasha M. A. Qadar
Published: April 2016

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ‐induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a‐h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR‐γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side‐effects.
Inhaled corticosteroids and HPA axis suppression: how important is it and how should it be managed?
Authors: Rao Bondugulapati L. N. , Rees D. A.
Published: April 2016

Inhaled corticosteroids (ICS) are established as a cornerstone of management for patients with bronchoconstrictive lung disease. However, systemic absorption may lead to suppression of the hypothalamic–pituitary–adrenal (HPA) axis in a significant minority of patients. This is more likely in ‘higher risk’ patients exposed to high cumulative ICS doses, and in those treated with frequent oral corticosteroids or drugs which inhibit cytochrome p450 3A4. Hypothalamic–pituitary–adrenal axis suppression is frequently unrecognized, such that some patients, notably children, only come to light when an adrenal crisis is precipitated by physical stress. To minimize this risk, ‘higher risk’ patients and those with previously identified suppressed cortisol responses to Synacthen testing should undergo an education programme to inform them about sick day rules. A review of ICS therapy should also be undertaken to ensure that the dose administered is the minimum required to control symptoms.
Insights into 6q21‐q22: Refinement of the critical region for acro‐cardio‐facial syndrome
Authors: Milani Donatella , Cagnoli Giulia Anna , Baccarin Marco , Alfei Enrico , Guerneri Silvana , Esposito Susanna
Published: April 2016

Deletions on chromosome 6q are rarely reported in the literature, and genotype‐phenotype correlations are poorly understood. We report a child with a deletion of the 6q21‐q22 chromosomal region, providing some intriguing results about the correlation between this region and acro‐cardio‐facial syndrome, congenital heart disease, split hand and foot malformation, and epilepsy.
Improving the colour fastness of dyed nylon‐6 fabric by graft copolymerisation and curing of acrylic acid
Authors: Mohaddes Farzad , Fergusson Stanley , Wang Lijing
Published: April 2016

The influence of grafting and grafting–curing of acrylic acid on the colour fastness of nylon‐6 fabric dyed with an acid dye of low wash fastness was investigated. The variables involved in grafting were initially optimised for pristine nylon‐6 fabric prior to grafting the same monomer onto the dyed fabrics. The highest graft yield achieved for the pristine and dyed nylon‐6 fabrics was 44 and 14% respectively. Grey scale testing and colorimetric analysis revealed that the highest colour fastness and the smallest drop in colour strength belonged to the dyed–grafted–cured nylon‐6 fabric. The colour components were measured, and the total colour difference of each sample after five washing cycles was computed. The specific colour difference showed that the implementation of either grafting or grafting–curing processes will alter the reference colour of the dyed fabric. The tensile strength of the grafted and grafted–cured fabrics was respectively 2.7 and 6.3% lower than that of dyed nylon‐6.
Benefit Sharing in a Global Context: Working Towards Solutions for Implementation
Authors: Hurst Daniel J.
Published: April 2016

Due to the state of globalized clinical research, questions have been raised as to what, if any, benefits those who contribute to research should receive. One model for compensating research participants is “benefit sharing,” and the basic premise is that, as a matter of justice, those who contribute to scientific research should share in its benefits. While incorporated into several international documents for over two decades, benefit sharing has only been sparsely implemented. This analysis begins by addressing the concept of benefit sharing, its historical development, and how it has been applied in the context of virus sharing for influenza research. The second portion of this analysis presents recommendations for ensuring benefit sharing. These recommendations are threefold: 1) an emphasis on social pressure, 2) the revision of international documents as means to ensure benefit sharing, and 3) greater collaboration between sponsor IRB and host country IRB. Because clinical research is a globalized industry, a global model will be proposed in the second that focuses on collaboration between the sponsor and host country. This collaboration is vital in order to ensure that proper forms of benefit sharing are accomplished as a matter of justice.
Association between gross motor function and nutritional status in children with cerebral palsy: a cross‐sectional study from Colombia
Authors: Herrera‐Anaya Elizabeth , Angarita‐Fonseca Adriana , Herrera‐Galindo Víctor M , Martínez‐Marín Rocío D P , Rodríguez‐Bayona Cindy N
Published: April 2016

Aim

To determine the association between gross motor function and nutritional status in children with cerebral palsy (CP) residing in an urban area in a developing country.

Method

We conducted a cross‐sectional study in 177 children (ages 2–12y, 59.3% male) with a diagnosis of CP who were attending rehabilitation centres in Bucaramanga, Colombia (2012–2013). A physiotherapist evaluated patients using the Gross Motor Function Classification System (GMFCS, levels I to V). Nutritional status was evaluated by nutritionists and classified according to the World Health Organization growth charts. We used linear and multinomial logistic regression methods to determine the associations.

Results

There were 39.5%, 6.8%, 5.6%, 16.4%, and 31.6% patients classified in levels I to V respectively. The mean adjusted differences for weight‐for‐age, height‐for‐age, BMI‐for‐age, and height‐for‐weight z‐scores were significantly larger for children classified in levels II to V compared with those in level I. The children classified in levels IV and V were more likely to have malnutrition (adjusted odds ratio [OR] 5.64; 95% confidence interval [CI] 2.27–14.0) and stunting (OR 8.42; 95% CI 2.90–24.4) than those classified in GMFCS levels I to III.

Interpretation

Stunting and malnutrition are prevalent conditions among paediatric patients with CP, and both are directly associated with higher levels of gross motor dysfunction.
London creditors and the fifteenth‐century depression
Authors: Stevens Matthew Frank
Published: April 2016

Evidence of debts owed to Londoners, and contested before the royal Court of Common Pleas, allows an examination of the role of London creditors in the English depression of the fifteenth century and a reassessment of its causes. In this article, four main issues are examined. What is the nature of the Court of Common Pleas evidence (section I)? What were the three main forms of credit offered by Londoners—unsecured cash loans, sales of goods on credit, and written instruments called bonds (section II)? What is yielded by decadal analysis of Londoners’ extension of credit in the fifteenth century—making direct comparisons with Nightingale's published Statute Merchant and Staple data (section III)? What defines, in modern economic terms, the claim of so‐called ‘monetarist’ historians that credit was actively withdrawn during the depression, and how is this verified by the actions of London creditors (section IV)? It is concluded that the records of the Court of Common Pleas provide the detailed evidence monetarist historians have previously lacked both to prove that Londoners actively withdrew credit during the fifteenth century and to demonstrate that they employed pure equilibrium credit rationing in order to do so.
Bending over forwards – to make a diagnosis
Authors: Hilton‐Jones D.
Published: April 2016

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