bluuebunny/crossref_metadata_2025 huggingface dataset:
The CLAVATA receptor FASCIATED EAR2 responds to different CLE peptides by signaling through different downstream effectors
Authors: Je Byoung Il , Xu Fang , Wu Qingyu , Liu Lei , Meeley Robert , Jackson David
Published: September 2017

Meristems contain groups of indeterminate stem cells that are critical for organ initiation throughout plant development. The shoot apical meristem (SAM) maintains itself and initiates all shoot organs, such as leaves, floral organs and axillary branch meristems. Development and balanced proliferation of the SAM is regulated by a feedback loop betweenCLAVATA(CLV) andWUSCHEL(WUS) signaling. CLV signaling is initiated by secretion of the CLV3 peptide ligand, which is perceived directly or indirectly by a number of Leucine-Rich-Repeat (LRR) receptor-like kinases, including CLV1 and BARELY ANY MERISTEM (BAM) 1-3, and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), as well as the receptor-like protein CLV2 in a complex with the CORYNE (CRN) pseudokinase. However, CLV2, and its maize ortholog FASCIATED EAR2 (FEA2) appear to function in signaling by several related CLV3/EMBRYO-SURROUNDING REGION (CLE) peptide ligands, including CLV3. Nevertheless, it remains unknown how CLV2 or FEA2 transmit specific signals from distinct CLE peptides. Here we show that FEA2 is involved in signaling from at least 2 distinct CLE peptides, ZmCLE7, a maize CLV3 ortholog, and ZmFON2-LIKE CLE PROTEIN1 (ZmFCP1), a newly identified CLE peptide functioning in SAM regulation. Signaling from these 2 different CLE peptides appears to be transmitted through 2 different candidate downstream effectors, COMPACT PLANT2 (CT2), the alpha subunit of the maize heterotrimeric G protein, and maize CRN. Our data provide a novel framework to understand how diverse signaling peptides can activate different downstream pathways through common receptor proteins.
Inferring processes of community assembly from macroscopic patterns: the case for inclusive and mechanistic approaches
Authors: Pontarp Mikael , Brännström Åke , Petchey Owen L
Published: September 2017

Statistical techniques exist for inferring community assembly processes from community patterns. Habitat filtering, competition, and biogeographical effects have, for example, been inferred from signals in phenotypic and phylogenetic data. The usefulness of current inference techniques is, however, debated as the causal link between process and pattern is often lacking and processes known to be important are ignored. Here, we revisit current knowledge on community assembly across scales and, in line with several reviews that have outlined the features and challenges associated with current inference techniques, we identify a discrepancy between features of real communities and current inference techniques. We argue, that mechanistic eco-evolutionary models in combination with novel model fitting and model evaluation techniques can provide avenues for more accurate, reliable and inclusive inference. To exemplify, we implement a trait-based and spatially explicit dynamic eco-evolutionary model and discuss steps of model modification, fitting, and evaluation as an iterative approach enabling inference from diverse data sources. This suggested approach can be computationally intensive, and model fitting and parameter estimation can be challenging. We discuss optimization of model implementation, data requirements and availability, and Approximate Bayesian Computation (ABC) as potential solutions to challenges that may arise in our quest for better inference techniques.
Sub-threshold resonance organizes activity and optimizes learning in neural networks
Authors: Roach James P. , Pidde Aleksandra , Katz Eitan , Wu Jiaxing , Ognjanovski Nicolette , Aton Sara J. , Zochowski Michal R.
Published: September 2017

Network oscillations across and within brain areas are critical for learning and performance in memory tasks. While a large amount of work has focused on the generation of neural oscillations, their effects on neuronal populations’ spiking activity and information encoding is less known. Here, we use computational modeling andin vivorecording to demonstrate that a shift in sub-threshold resonance can interact with oscillating input to ensure that networks of neurons properly encode new information represented in external inputs to the weights of recurrent synaptic connections. Using a neuronal network model, we find that due to an input-current dependent shift in their resonance response, individual neurons in a network will arrange their phases of firing to represent varying strengths of their respective inputs. As networks encode information, neurons fire more synchronously, and this effect limits the extent to which further “learning” (in the form of changes in synaptic strength) can occur. We also demonstrate that sequential patterns of neuronal firing can be accurately stored in the network; these sequences are later reproduced without external input (in the context of sub-threshold oscillations) in both the forward and reverse directions (as has been observed following learningin vivo). To test whether a similar mechanism could actin vivo, we show that periodic stimulation of hippocampal neurons coordinates network activity and functional connectivity in a frequency-dependent manner. We conclude that sub-threshold resonance provides a plausible network-level mechanism to accurately encode and retrieve information without over-strengthening connections between neurons.
Spatially uniform establishment of chromatin accessibility in the earlyDrosophilaembryo
Authors: Haines Jenna E. , Eisen Michael B.
Published: September 2017

As theDrosophilaembryo transitions from the use of maternal RNAs to zygotic transcription, domains of open chromatin, with relatively low nucleosome density and specific histone marks, are established at promoters and enhancers involved in patterned embryonic transcription. However, it remains unclear whether open chromatin is a product of activity - transcription at promoters and patterning transcription factor binding at enhancers - or whether it is established by independent mechanisms. Recent work has implicated the ubiquitously expressed, maternal factor Zelda in this process. To assess the relative contribution of activity in the establishment of chromatin accessibility, we have probed chromatin accessibility across the anterior-posterior axis of earlyDrosophila melanogasterembryos by applying a transposon based assay for chromatin accessibility (ATAC-seq) to anterior and posterior halves of hand-dissected, cellular blastoderm embryos. We find that genome-wide chromatin accessibility is remarkably similar between the two halves. Promoters and enhancers that are active in exclusively one half of the embryo have open chromatin in the other half, demonstrating that chromatin accessibility is not a direct result of activity. However, there is a small skew at enhancers that drive transcription exclusively in either the anterior or posterior half of the embryo, with greater accessibility in the region of activity. Taken together these data support a model in which regions of chromatin accessibility are defined and established by ubiquitous factors, and fine-tuned subsequently by activity.
An insight into the synthesis, crystal structure, geometrical modelling of crystal morphology, Hirshfeld surface analysis and characterization ofN-(4-methylbenzyl)benzamide single crystals
Authors: Goel Sahil , Yadav Harsh , Sinha Nidhi , Singh Budhendra , Bdikin Igor , Rao Devarapalli Chenna , Gopalaiah Kovuru , Kumar Binay
Published: September 2017

A versatile approach for the synthesis ofN-(4-methylbenzyl)benzamide, C15H15NO, using CuI as catalyst has been reported. Single crystals of the synthesized compound were grown using the slow evaporation solution technique. The crystal structure of theN-(4-methylbenzyl)benzamide crystals has been determined by single-crystal X-ray diffraction. The compound crystallizes in an orthorhombic lattice, noncentrosymmetric space groupPna21. The crystal structure is stabilized by intermolecular N—H...O hydrogen bonds and weak C—H...π interactions to form layers parallel to theaaxis. A user-friendly approach based on centre of mass propagation vector theory was used to predict the crystal morphology. The framework developed here utilizes the concept of intermolecular bond strength to discern the crystal morphology. Fourier transform IR, NMR and high-resolution mass spectrometry analytical techniques were used for the identification of functional groups and confirmation of the structure of the title compound. All of the intermolecular interactions present in the crystal structure, including the C—H...π, C—H...O and N—H...O interactions, were investigated and confirmed by molecular Hirshfeld surface analysis. From linear optical spectroscopy, the transmittance, optical band gap and UV cutoff wavelength were determined. The photoluminescence emission spectrum was recorded for a grown crystal. Dielectric measurements were performed at room temperature for various frequencies. The mechanical strength of the (001) plane of the title compound was measured using the Vickers micro-hardness technique. A piezo-coefficient of 15 pC N−1was found along the (001) plane of the title crystals. The thermal stability and melting point were also investigated. In addition, density functional theory simulations were used to calculate the optimized molecular geometry and the UV–vis spectrum, and to determine the highest occupied molecular orbital/lowest unoccupied molecular orbital energy gap. The results show thatN-(4-methylbenzyl)benzamide is a potential candidate for multifunctional optical and piezoelectric crystals.
Nanocrystallography measurements of early stage synthetic malaria pigment
Authors: Dilanian Ruben A. , Streltsov Victor , Coughlan Hannah D. , Quiney Harry M. , Martin Andrew V. , Klonis Nectarios , Dogovski Con , Boutet Sébastien , Messerschmidt Marc , Williams Garth J. , Williams Sophie , Phillips Nicholas W. , Nugent Keith A. , Tilley Leann , Abbey Brian
Published: September 2017

The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.
Morphological and crystallographic anisotropy of severely deformed commercially pure aluminium by three-dimensional electron backscatter diffraction
Authors: Naghdy Soroosh , Pirgazi Hadi , Verleysen Patricia , Petrov Roumen , Kestens Leo
Published: September 2017

The aim of this paper is to examine the morphological and crystallographic anisotropy that develops during high-pressure torsion (HPT) processing. Commercially pure aluminium was subjected to monotonic HPT deformation at room temperature. The microstructure and texture were studied by large-area electron backscatter diffraction (EBSD) scans. Three-dimensional EBSD scans served to scrutinize the morphological anisotropy and local texture. It was observed that two distinct stages of grain fragmentation and saturation occur during processing. Grains exhibited an ellipsoidal shape rather than an equi-axed one. The major axes of the ellipsoids showed a favorable orientation at the steady-state stage: an almost 20° inclination towards the shear direction. The global texture was characterized by typical shear components of face-centered cubic metals at both stages. However, the local texture revealed a preferential fragmentation pattern in the first stage: orientations in the vicinity of ideal fibers became less heavily fragmented while non-ideal orientations broke up more severely. This phenomenon was linked with the lattice rotation required to bring an initial orientation close to a stable one. Although the texture weakened considerably in the fragmentation stage, the texture index did not further decrease in the saturation stage. Saturation of texture, grain refinement and formation of microstructure are discussed in the light of different microstructural coarsening mechanisms.
EAACI Guidelines on allergen immunotherapy: IgE‐mediated food allergy
Authors: Pajno G. B. , Fernandez‐Rivas M. , Arasi S. , Roberts G. , Akdis C. A. , Alvaro‐Lozano M. , Beyer K. , Bindslev‐Jensen C. , Burks W. , Ebisawa M. , Eigenmann P. , Knol E. , Nadeau K. C. , Poulsen L. K. , van Ree R. , Santos A. F. , du Toit G. , Dhami S. , Nurmatov U. , Boloh Y. , Makela M. , O'Mahony L. , Papadopoulos N. , Sackesen C. , Agache I. , Angier E. , Halken S. , Jutel M. , Lau S. , Pfaar O. , Ryan D. , Sturm G. , Varga E.‐M. , van Wijk R. G. , Sheikh A. , Muraro A. ,   EAACI Allergen Immunotherapy Guidelines Group
Published: September 2017

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.
Families’ perceived benefits of home visits for managing paediatric obesity outweigh the potential costs and barriers
Authors: Gehring Nicole D. , Ball Geoff D. C. , Perez Arnaldo , Holt Nicholas L. , Neuman Daniel , Spence Nicholas , Mercier Laura , Jetha Mary
Published: September 2017

Aim

Home visits have successfully been used to deliver various health services, but what role could they play in paediatric weight management? Low treatment initiation and high attrition prompted our multidisciplinary paediatric weight management clinic to investigate how families perceived the benefits and barriers of home visits.

Methods

We focused on children with obesity aged 2–17 who were enrolled in our tertiary‐level clinic in Alberta, Canada. None had received a home visit. The families were interviewed face‐to‐face from October 2015 to October 2016, and we used a qualitative description methodological framework and manifest content analysis. The parents were the main interviewees.

Results

Of the 56 families, 89% were interested in a home visit, 82% wanted support from a dietician and 54% from an exercise specialist. The perceived benefits of home visits included comprehensive assessment (95%), convenience (86%), tailored care (29%) and family involvement (13%), while the costs and barriers included clinicians’ potential judgmental attitudes (30%), loss of privacy (19%) and distractions (10%). Some thought clinicians would find home visits inconvenient (25%), with bureaucratic challenges (14%) and sustainability issues (5%).

Conclusion

Families felt home visits were a convenient option for managing paediatric obesity and identified important benefits and barriers that could guide such interventions.
Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria
Authors: Cermak Pavel , Olsovska Jana , Mikyska Alexandr , Dusek Martin , Kadleckova Zuzana , Vanicek Jiri , Nyc Otakar , Sigler Karel , Bostikova Vanda , Bostik Pavel
Published: September 2017

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic‐associated diarrhoea. Treatment of C. difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B. fragilis, C. perfringens and C. difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C. difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15–107 μg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains.
A cartography of the possible: Reflections on militant ethnography in and against the edu‐factory
Authors: Pusey André
Published: September 2017

This paper examines militant research through the lens of several challenges the author faced when experimenting with it as part of their PhD research. It engages with ongoing debates about the role and complexity of militant methodologies within‐against‐beyond the university. Specifically it suggests that the political economy of the academy is a challenge to militant research through the growing influence of the law of value within increasingly marketised academic contexts. The paper argues that the academic‐recuperation‐machine has the potential to assimilate what it terms the “minor knowledge” created through militant research within its circuits of institutionalisation and commodification, becoming just another output or tool in the toolbox. Relatedly it suggests these challenges do not simply require a reflection on positionality vis‐à‐vis academia/activism, but a collective struggle around academic labour in against‐beyond the university and how militant researcher might remain “in but not of” the neoliberal university.
Frame Rate vs Resolution: A Subjective Evaluation of Spatiotemporal Perceived Quality Under Varying Computational Budgets
Authors: Debattista K. , Bugeja K. , Spina S. , Bashford‐Rogers T. , Hulusic V.
Published: September 2017

Maximizing performance for rendered content requires making compromises on quality parameters depending on the computational resources available . Yet, it is currently unclear which parameters best maximize perceived quality. This work investigates perceived quality across computational budgets for the primary spatiotemporal parameters of resolution and frame rate. Three experiments are conducted. Experiment 1 (n = 26) shows that participants prefer fixed frame rates of 60 frames per second (fps) at lower resolutions over 30 fps at higher resolutions. Experiment 2 (n = 24) explores the relationship further with more budgets and quality settings and again finds 60 fps is generally preferred even when more resources are available. Experiment 3 (n = 25) permits the use of adaptive frame rates, and analyses the resource allocation across seven budgets. Results show that while participants allocate more resources to frame rate at lower budgets the situation reverses once higher budgets are available and a frame rate of around 40 fps is achieved. In the overall, the results demonstrate a complex relationship between frame rate and resolution's effects on perceived quality. This relationship can be harnessed, via the results and models presented, to obtain more cost‐effective virtual experiences.
Increased adult neurogenesis associated with reactive astrocytosis occurs prior to neuron loss in a mouse model of neurodegenerative disease
Authors: Liu Ting‐Ting , Ye Xiao‐Lian , Zhang Jin‐Ping , Yu Ting‐Ting , Cheng Shan‐Shan , Zou Xiao‐Chuan , Xu Yun , Chen Gui‐Quan , Yin Zhen‐Yu
Published: September 2017

Aims

This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display.

Methods and Results

Forebrain‐specific nicastrin (NCT) conditional knockout (cKO) mice were generated by crossing NCTf/f with CaMKIIα‐Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells (NPCs). Immunohistochemistry (IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin (DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss.

Conclusions

NCT‐dependent γ‐secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease.
Schisandrin B down‐regulated lncRNA BCYRN1 expression of airway smooth muscle cells by improving miR‐150 expression to inhibit the proliferation and migration of ASMC in asthmatic rats
Authors: Zhang Xiao‐yu , Tang Xue‐yi , Ma Li‐jun , Guo Ya‐li , Li Xiao‐su , Zhao Li‐min , Tian Cui‐jie , Cheng Dong‐Jun , Chen Zhuo‐chang , Zhang Luo‐xian
Published: September 2017

Objective

The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored.

Methods

SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR‐150 and lncRNA BCYRN1 levels were measured by qRT‐PCR. The combination of BCYRN1 and miR‐150 was detected by RNA pull down. ASMCs’ viability/proliferation/migration were examined by WST‐1 assay and 24‐well Transwell system.

Results

Schisandrin B up‐regulated miR‐150 expression and down‐regulated BCYRN1 expression in sensitized rats. Schisandrin B reversed the expression of miR‐150 and BCYRN1 in MV‐treated ASMCs. In addition, Schisandrin B inhibited the viability, proliferation and migration of MV‐induced ASMCs. We also found miR‐150 inhibited BCYRN1 expression which was proved by experiments using ASMCs transfected with miR‐150 inhibitor.

Conclusion

Schisandrin B increased miR‐150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR‐150, which indicated that Schisandrin B could regulate BCYRN1 through miR‐150.
Expression of connexin 43 in the human hair follicle: emphasis on the connexin 43 protein levels in the bulge and through the keratinization process
Authors: Flores Angel Fernandez , Varela‐Vazquez Adrian , Mayan Maria D. , Fonseca Eduardo
Published: September 2017

Background

Gap junctions form communication compartments between cells. These channels assemble from connexin subunits.

Objective

To investigate the immunoexpression of connexin 43 (Cx43) in adult human hair follicles.

Methods

Cases were retrospectively obtained from our archives.

Results

We identified immunoexpression of Cx43 in the matrix, the papilla, the outer root sheath, the bulge, the medulla, the cortex, the shaft and the secretory part of the sebaceous gland. There was very low expression (VLE) of Cx43 in the perifollicular sheath, the mantle and the arrector pili muscle. The internal root sheath showed high‐density expression in the bulb. Such expression abruptly decreased at different points in each of its layers at the point of keratinization. The isthmus showed Cx43‐positive staining in the middle layers and all along, whereas there was VLE in the two outermost layers. The infundibulum showed expression all along the middle layers, whereas it showed VLE in the 2 outermost layers and in the 2 or 3 innermost layers.

Conclusions

The bulge contains Cx43. Our results suggest that keratinization in the hair follicle is closely related to the decrease in Cx43 expression.
Phenotypic plasticity in the morphology of small benthic Icelandic Arctic charr (Salvelinus alpinus)
Authors: Kristjánsson Bjarni K. , Leblanc Camille A.‐L. , Skúlason Skúli , Snorrason Sigurður S. , Noakes David L.G.
Published: September 2017

Intraspecific phenotypic diversity is the raw material for evolution, so understanding its origin and maintenance is critically important for conservation of biodiversity. Intraspecific diversity in a trait or a suite of traits can result from genetic diversity and/or phenotypic plasticity. The two are, however, not independent as plasticity has been shown to evolve. In this study, we evaluated the importance of phenotypic plasticity in generating morphological diversity in populations of small benthic Arctic charr in Iceland, using a rearing experiment with contrasting modes of feeding. We also examined the association between phenotypic plasticity in offspring groups generated by the contrasting feeding modes and important ecological variables characterising the natural habitats of the respective populations. Although the level of plasticity could not be related to any of the ecological measurements, clear differences in morphological reaction norms among populations suggest that plasticity is an important aspect of morphological diversity of the charr. It is not clear whether that plasticity is adaptive, but it is notable that reaction norms in all populations have similar reaction to the treatments.
Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia
Authors: Gudbrandsdottir Sif , Brimnes Marie , Køllgaard Tania , Hasselbalch Hans C , Nielsen Claus H
Published: September 2017

Objective

To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM).

Methods

Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell‐surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL‐6 and IL‐10 were measured by flow cytometry.

Results

PBMCs from ITP patients at baseline contained a lower proportion of IL‐10+ B cells (P < .01) and IL‐6+ B cells (P < .01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5+ B cells increased (P < .01) and CD27+ memory B cells decreased (P < .05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = −0.71; P < .05).

Conclusion

Both treatment regimens normalized the frequencies of cytokine‐producing B cells. The additional increase in CD5+ B cells after RTX+DXM is compatible with induction of Bregs.
Using spatiotemporal source separation to identify prominent features in multichannel data without sinusoidal filters
Authors: Cohen Michael X
Published: September 2017

The number of simultaneously recorded electrodes in neuroscience is steadily increasing, providing new opportunities for understanding brain function, but also new challenges for appropriately dealing with the increase in dimensionality. Multivariate source separation analysis methods have been particularly effective at improving signal‐to‐noise ratio while reducing the dimensionality of the data and are widely used for cleaning, classifying and source‐localizing multichannel neural time series data. Most source separation methods produce a spatial component (that is, a weighted combination of channels to produce one time series); here, this is extended to apply source separation to a time series, with the idea of obtaining a weighted combination of successive time points, such that the weights are optimized to satisfy some criteria. This is achieved via a two‐stage source separation procedure, in which an optimal spatial filter is first constructed and then its optimal temporal basis function is computed. This second stage is achieved with a time‐delay‐embedding matrix, in which additional rows of a matrix are created from time‐delayed versions of existing rows. The optimal spatial and temporal weights can be obtained by solving a generalized eigendecomposition of covariance matrices. The method is demonstrated in simulated data and in an empirical electroencephalogram study on theta‐band activity during response conflict. Spatiotemporal source separation has several advantages, including defining empirical filters without the need to apply sinusoidal narrowband filters.
Who Are Heritage Writers? Language Experiences and Writing Proficiency
Authors: Gatti Alberta , O'Neill Teresa
Published: September 2017

This article explores the relationship between the writing proficiency of heritage speakers of Mandarin Chinese, Korean, and Spanish and their context of acquisition, educational experiences, and language practices. Biographical data and proficiency ratings obtained with the ACTFL Writing Proficiency Test were collected for 187 adult heritage speakers. These data are analyzed in order to shed light on connections between the writing proficiency of heritage speakers of these three languages and their language experiences, which have implications for placement and pedagogy in the postsecondary setting. The results of the analysis are then deployed in a series of recommendations to support the development of writing proficiency in the classroom. The authors advocate a proficiency‐oriented approach to the teaching of heritage language that leverages the learners’ linguistic resources.
Using Resin‐Based 3D Printing to Build Geometrically Accurate Proxies of Porous Sedimentary Rocks
Authors: Ishutov Sergey , Hasiuk Franciszek J. , Jobe Dawn , Agar Susan
Published: September 2017

Three‐dimensional (3D) printing is capable of transforming intricate digital models into tangible objects, allowing geoscientists to replicate the geometry of 3D pore networks of sedimentary rocks. We provide a refined method for building scalable pore‐network models (“proxies”) using stereolithography 3D printing that can be used in repeated flow experiments (e.g., core flooding, permeametry, porosimetry). Typically, this workflow involves two steps, model design and 3D printing. In this study, we explore how the addition of post‐processing and validation can reduce uncertainty in the 3D‐printed proxy accuracy (difference of proxy geometry from the digital model). Post‐processing is a multi‐step cleaning of porous proxies involving pressurized ethanol flushing and oven drying. Proxies are validated by: (1) helium porosimetry and (2) digital measurements of porosity from thin‐section images of 3D‐printed proxies. 3D printer resolution was determined by measuring the smallest open channel in 3D‐printed “gap test” wafers. This resolution (400 µm) was insufficient to build porosity of Fontainebleau sandstone (∼13%) from computed tomography data at the sample's natural scale, so proxies were printed at 15‐, 23‐, and 30‐fold magnifications to validate the workflow. Helium porosities of the 3D‐printed proxies differed from digital calculations by up to 7% points. Results improved after pressurized flushing with ethanol (e.g., porosity difference reduced to ∼1% point), though uncertainties remain regarding the nature of sub‐micron “artifact” pores imparted by the 3D printing process. This study shows the benefits of including post‐processing and validation in any workflow to produce porous rock proxies.
Acquired haemophilia in cancer: A systematic and critical literature review
Authors: Napolitano M. , Siragusa S. , Mancuso S. , Kessler C. M.
Published: September 2017

Aim

There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer.

Methods

Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding.

Results

Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37‐86 years) and females (range 43‐89 years), 39 patients were female subjects and 66 were males. A solid cancer was diagnosed in 60 subjects, while 45 patients suffered a haematological malignancy. Solid cancers affected mainly males; however, the incidence of solid tumours vs haematological malignancies was not statistically significant (P = .09). Not all patients were treated for their underlying cancer, bleeding and/or inhibitor, in two cases outcome is unavailable. CR was reported in 62.1% (64/103) cases, PR in 9.7% (10/103) cases, NR with or without death was reported in 28.1% (29/103) cases.

Conclusion

CR was best achieved when successful and complete elimination of autoantibodies occurred contemporaneously with the successful treatment of the underlying malignancy. In some cases, recurrent autoantibodies were harbingers of relapsed cancer. Type of cancer, inhibitor titer, treatments administered for bleeding control and inhibitor eradication did not significantly affect clinical outcome of analyzed cases.
The value of intramural vascular invasion in colorectal cancer – a systematic review and meta‐analysis
Authors: Knijn Nikki , van Exsel Ursula E M , de Noo Mirre E , Nagtegaal Iris D
Published: September 2017

Extramural venous invasion (EMVI) is a well‐known prognostic factor in colorectal cancer (CRC). Vascular invasion within the bowel wall, intramural vascular invasion (IMVI), has received less attention and its incidence and prognostic importance in CRC is not completely known. A systematic literature search was performed focusing on the impact of IMVI in CRC. Data were analysed using Review Manager version 5.3 on incidence and clinical endpoints local recurrence, 5‐year cancer‐specific survival (CSS) and 5‐year overall survival (OS). Meta‐analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). Of the initial 1199 papers identified by our search strategy, 20 were included in this meta‐analysis. Of the 8078 included patients, 1008 patients had IMVI (12.5%). Studies that re‐examined histological slides showed a higher incidence of IMVI compared to studies extracting IMVI from pathology reports (17.6 versus 7.7%, P < 0.001). Detection of IMVI increased significantly with the use of additional staining (22.9 versus 12.3%, P < 0.001). IMVI was associated with a decreased CSS HR: 1.6, 95% CI 1.2–2.2 in multivariate analysis). A borderline significant effect was observed for IMVI on local recurrence (RR: 1.5, 95% CI: 0.98–2.3) and OS (RR: 1.2, 95% CI: 1.0–1.4). In conclusion, despite the limited number of studies, there is a clear association with outcome in the presence of IMVI. This warrants more attention to this under‐reported prognostic factor.
Estimating currency misalignment using the Penn effect: It is not as simple as it looks
Authors: Cheung Yin‐Wong , Chinn Menzie , Nong Xin
Published: September 2017

We investigate the robustness of the Penn effect—the finding that the price level is higher in countries with a higher per capita income—over different samples, measures, and specifications. Testing for the Penn effect has been hampered by the imprecision of the price measures, so that use of different versions of the data set can lead to substantially different results. We find that the price level‐income elasticity is fairly consistently estimated across data sets. However, there is some evidence that the relationship is non‐linear. For developed economies, the quadratic term implies an inverted U‐shaped relationship. Developing economies, on the other hand, display a U‐shaped relationship. Estimates of misalignment differ, depending on the choice of specification and data sets. It appears that the Renminbi (RMB) was fairly valued by 2011. In contrast, the RMB's value was undervalued in 2005, and overvalued in 2014.
Systematic psychometric review of self‐reported instruments to assess patient safety culture in primary care
Authors: Desmedt Melissa , Bergs Jochen , Vertriest Sonja , Vlayen Annemie , Schrooten Ward , Hellings Johan , Vandijck Dominique
Published: September 2017

Aims

To give an overview of empirical studies using self‐reported instruments to assess patient safety culture in primary care and to synthesize psychometric properties of these instruments.

Background

A key condition for improving patient safety is creating a supportive safety culture to identify weaknesses and to develop improvement strategies so recurrence of incidents can be minimized. However, most tools to measure and strengthen safety culture have been developed and tested in hospitals. Nevertheless, primary care is facing greater risks and a greater likelihood of causing unintentional harm to patients.

Design

A systematic literature review of research evidence and psychometric properties of self‐reported instruments to assess patient safety culture in primary care.

Data Sources

Three databases until November 2016.

Review Methods

The review was carried out according to the protocol for systematic reviews of measurement properties recommended by the COSMIN panel and the PRISMA reporting guidelines.

Results

In total, 1.229 records were retrieved from multiple database searches (Medline = 865, Web of Science = 362 and Embase = 2). Resulting from an in‐depth literature search, 14 published studies were identified, mostly originated from Western high‐income countries. As these studies come with great diversity in tools used and outcomes reported, comparability of the results is compromised. Based on the psychometric review, the SCOPE‐Primary Care survey was chosen as the most appropriate instrument to measure patient safety culture in primary care as the instrument had excellent internal consistency with Cronbach's alphas ranging from 0.70‐0.90 and item factor loadings ranging from 0.40‐0.96, indicating a good structural validity.

Conclusion

The findings of the present review suggest that the SCOPE‐Primary Care survey is the most appropriate tool to assess patient safety culture in primary care. Further psychometric techniques are now essential to ensure that the instrument provides meaningful information regarding safety culture.
Ancient mitochondrial genomes reveal the demographic history and phylogeography of the extinct, enigmatic thylacine (Thylacinus cynocephalus)
Authors: White Lauren C. , Mitchell Kieren J. , Austin Jeremy J.
Published: September 2017

Aim

The Tasmanian tiger, or thylacine, is an infamous example of a recent human‐mediated extinction. Confined to the island of Tasmania in historical times, thylacines were hunted to extinction <150 years after European arrival. Thylacines were also once widespread across the Australian mainland, but became extinct there c. 3,200 years before present (bp). Very little is known about thylacine biology and population history; the cause of the thylacines extirpation from the mainland is still debated and the reasons for its survival in Tasmania into the 20th century are unclear. In this study, we investigate the thylacine's phylogeography and demographic history leading up to their extinction on both the mainland and Tasmania to gain insight into this enigmatic species.

Location

Southern Australia.

Methods

We generated 51 new thylacine mitochondrial DNA (mtDNA) genome sequences from sub‐fossil remains and historical museum specimens, and analysed them to reconstruct the species’ phylogeography and demographic history.

Results

We found evidence that thylacines had contracted into separate eastern and western populations prior to the Last Glacial Maximum (c. 25,000 yr bp), and that the ancient western population was larger and more genetically diverse than the historical Tasmanian population. At the time of European arrival in c. 1800 CE, Tasmanian thylacines had limited mtDNA diversity, possibly resulting from a bottleneck event broadly coincident with an El Niño‐Southern Oscillation (ENSO) associated climate event, although we find some indication that the population was expanding during the late Holocene.

Main Conclusions

The timing of this putative expansion, in concert with a climate event, suggests that climate change had an influence on thylacine population dynamics. Given that ENSO effects are known to have been more severe on mainland Australia, we suggest that climate change, in synergy with other drivers, is likely to have contributed to the thylacine mainland extinction.
Real world MRI experience with nonconditional and conditional cardiac rhythm devices after MagnaSafe
Authors: Mason Steve , Osborn Jeffrey S. , Dhar Ritesh , Tonkin Allison , Ethington Jon‐David , Le Viet , Benuzillo Jose , Lappe Donald L. , Knowlton Kirk U. , Bunch T. Jared , Anderson Jeffrey L.
Published: September 2017

Introduction

The recent MagnaSafe Registry demonstrated safety of nonthoracic magnetic resonance imaging (MRI) with nonconditional cardiac implantable electronic devices (CIEDs). However, independent validation and extension to thoracic MRIs are needed.

Methods and results

We prospectively examined 178 consecutive patients with CIEDs who underwent 212 MRI scans (62 with implantable cardioverter/defibrillators) for clinical reasons between February 2014 and August 2016. Scans were done in standard modes with a limit of 2 W/kg. Pacing modes were ODO or OVO for intrinsic rates > 40 and DOO or VOO for rates ≤ 40. Patients were cleared prescan by both radiology and cardiology, and pre‐ and postscan CIED interrogations were performed. Primary outcome events were death and generator or lead failure. Secondary events included battery voltage loss > 0.04 V, decrease in P wave voltage > 50% or R wave voltage > 25%, threshold increase of > 0.5 V, and impedance change > 50 Ω. Scan sites were 87 (41%) C‐spine/head/neck, 28 (13%) T‐spine/cardiac/shoulder (thoracic), 69 (33%) L‐spine/abdomen/pelvis, and 28 (13%) lower extremity. No primary or secondary outcome events occurred, and no periscan disruption of pacing was noted.

Conclusion

In a real‐world MRI experience in patients with CIEDs representing a broad range of models, types, and scan sites (including thoracic scans), no adverse safety signals were noted. This experience validates and extends that of the large but inclusion‐restricted MagnaSafe Registry, profiles MRI scanning in CIED patients in general clinical practice, and argues against replacing nonconditional with conditional devices when MRI is performed in a carefully controlled environment.
Real‐world treatment patterns and clinical outcomes in advanced cutaneous melanoma patients in France
Authors: Sassolas B. , Leccia M.T. , Godard C. , Benmahamed L. , Flinois A. , Levy‐Bachelot L. , Bédane C.
Published: September 2017

Background

Since 2011, the management of advanced melanoma has radically changed with the availability of new therapies (immunotherapy and BRAF‐targeted therapy) and with BRAF testing.

Objectives

Following the introduction of these new therapies, the objectives of this AMEL study were to describe treatment patterns and evaluate overall survival (OS) among unresectable stage III/IV melanoma patients, in a real‐life setting in France.

Methods

The AMEL study is a multicentre retrospective record review study. Thirty‐three physicians working in 33 unique treatment centres participated in the study. Two hundred and sixty‐four patients diagnosed between 1 January 2012 and 31 October 2012 with unresectable stage III/IV melanoma were included in the study.

Results

94.7% of the patients received a first‐line antitumour drug treatment, 62.5% a second‐line treatment while 26.9% received a third‐line treatment with no significant differences between patients with a BRAF mutation (50.4%) and BRAF wild type (47.0%).

First‐line treatment differs according to the BRAF status: 74.8% of patients with a BRAF mutation received a BRAF inhibitor while 79.3% of the BRAF wild‐type patients were treated with conventional chemotherapy. In second line and over, the treatment patterns were more heterogeneous, depending on the BRAF mutation, the treatment received previously, the speed of progression of the disease and the availability of immunotherapy at the time the treatment was initiated.

Conclusion

Regardless of the BRAF mutation status, the median OS of patients was 16 months (95% CI = 14–18). Compared to a similar study conducted in 2007 (MELODY), a gain of 4 months is observed. The gain seems to be higher for patients with a BRAF mutation (18 months) than for those without a BRAF mutation (14 months). The OS of patients who sequentially received both a BRAF inhibitor and ipilimumab (28 months) highlights the benefit of this treatment sequence.