bluuebunny/crossref_metadata_2025 huggingface dataset:
A data-driven model for the assessment of Tuberculosis transmission in evolving demographic structures
Authors: Arregui Sergio , Iglesias María José , Samper Sofía , Marinova Dessislava , Martín Carlos , Sanz Joaquín , Moreno Yamir
Published: March 2017

In the case of tuberculosis (TB), the capabilities of epidemic models to produce quantitatively robust forecasts are limited by multiple hindrances. Among these, understanding the complex relationship between disease epidemiology and populations' age structure has been highlighted as one of the most relevant. TB dynamics depends on age in multiple ways, some of which are traditionally simplified in the literature. That is the case of the heterogeneities in contact intensity among different age-strata that are common to all air-borne diseases, but still typically neglected in the TB case. Furthermore, whilst demographic structures of many countries are rapidly aging, demographic dynamics is pervasively ignored when modeling TB spreading. In this work, we present a TB transmission model that incorporates country-specific demographic prospects and empirical contact data around a data-driven description of TB dynamics. Using our model, we find that the inclusion of demographic dynamics is followed by an increase in the burden levels prospected for the next decades in the areas of the world that are most hit by the disease nowadays. Similarly, we show that considering realistic patterns of contacts among individuals in different age-strata reshapes the transmission patterns reproduced by the models, a result with potential implications for the design of age-focused epidemiological interventions.

Significance Statement

Even though tuberculosis (TB) is acknowledged as a strongly age-dependent disease, it remains unclear how TB epidemics would react, in the following decades, to the generalized aging that human populations are experiencing worldwide. This situation is partly caused by the limitations of current transmission models at describing the relationship between demography and TB transmission. Here, we present a data-driven epidemiological model that, unlike previous approaches, explicitly contemplates relevant aspects of the coupling between agestructure and TB dynamics, such as demographic evolution and contact heterogeneities. Using our model, we identify substantial biases in epidemiological forecasts rooted in an inadequate description of these aspects, both at the level of aggregated incidence and mortality rates and their distribution across age-strata.
A Bayesian Framework for Estimating Cell Type Composition from DNA Methylation Without the Need for Methylation Reference
Authors: Rahmani Elior , Schweiger Regev , Shenhav Liat , Wingert Theodora , Hofer Ira , Gabel Eilon , Eskin Eleazar , Halperin Eran
Published: March 2017

We introduce a Bayesian semi-supervised method for estimating cell counts from DNA methylation by leveraging an easily obtainable prior knowledge on the cell type composition distribution of the studied tissue. We show mathematically and empirically that alternative methods which attempt to infer explicit cell counts without methylation reference can only capture linear combinations of cell counts rather than provide one component per cell type. Our approach, which allows the construction of a set of components such that each component corresponds to a single cell type, therefore provides a new opportunity to investigate cell compositions in genomic studies of tissues for which it was not possible before.
Face inversion reveals holistic processing of peripheral faces
Authors: Kovács Petra , Knakker Balázs , Hermann Petra , Kovács Gyula , Vidnyánszky Zoltán
Published: March 2017

Face perception is accomplished by face-selective neural processes, involving holistic processing that enables highly efficient integration of facial features into a whole face representation. It has been shown that in face-selective regions of the ventral temporal cortex, neural resources involved in holistic processing are primarily dedicated to the central portion of the visual field. These findings raise the intriguing possibility that holistic processing might be the privilege of centrally presented faces and could be strongly diminished in the case of peripheral faces. We addressed this question using the face inversion effect, a well established marker of holistic face processing. The behavioral results revealed impaired identity discrimination performance for inverted peripheral faces scaled according to the V1 magnification factor, compared to upright presented faces. The size of peripheral face inversion effect (FIE) was comparable to that found for centrally displayed faces. Face inversion affected the early ERP responses to faces in two time intervals. The earliest FIE was most pronounced in the time window between 130-140 ms following stimulus presentation, for both centrally and peripherally displayed faces and in the latter case, it was present only over the contralateral hemisphere. The timing of the next component FIE corresponded closely with the temporal interval of the N170 ERP component and showed strong right hemisphere lateralization, both when faces were displayed in the left or right visual field. Furthermore, we also showed that centrally presented face masks impaired peripheral face identity discrimination performance, but did not reduce the magnitude of the FIE. These findings revealed robust behavioral and neural inversion effects for peripheral faces and thus suggest that faces are processed holistically throughout the visual field.

Highlights

Robust behavioral and neural inversion effect was found for peripheral faces.

P1 ERP component is modulated by inverted central and contralateral faces.

N170 ERP component is modulated by centrally and peripherally presented faces.

Neural face inversion effect shows strong right hemisphere lateralization.

Faces are processed holistically throughout the visual field.
orcomutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants
Authors: Trible Waring , Chang Ni-Chen , Matthews Benjamin J , McKenzie Sean K , Olivos-Cisneros Leonora , Oxley Peter R , Saragosti Jonathan , Kronauer Daniel JC
Published: March 2017

Life inside ant colonies is orchestrated with a diverse set of pheromones, but it is not clear how ants perceive these social cues. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here we generate the first mutant lines in ants by disruptingorco, a gene required for the function of all ORs. We find thatorcomutants exhibit severe deficiencies in social behavior and fitness, suggesting that they are unable to perceive pheromones. Surprisingly, unlike inDrosophila melanogaster,orcomutant ants also lack most of the approximately 500 antennal lobe glomeruli found in wild-types. These results illustrate that ORs are essential for ant social organization, and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain.
Functional Annotation of Chemical Libraries across Diverse Biological Processes
Authors: Piotrowski Jeff S. , Li Sheena C. , Deshpande Raamesh , Simpkins Scott W. , Nelson Justin , Yashiroda Yoko , Barber Jacqueline M. , Safizadeh Hamid , Wilson Erin , Okada Hiroki , Gebre Abraham A. , Kubo Karen , Torres Nikko P. , LeBlanc Marissa A. , Andrusiak Kerry , Okamoto Reika , Yoshimura Mami , DeRango-Adem Eva , van Leeuwen Jolanda , Shirahige Katsuhiko , Baryshnikova Anastasia , Brown Grant W. , Hirano Hiroyuki , Costanzo Michael , Andrews Brenda , Ohya Yoshikazu , Osada Hiroyuki , Yoshida Minoru , Myers Chad L. , Boone Charles
Published: March 2017

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells to a compound, revealing chemical-genetic interactions that can elucidate a compound’s mode of action. We developed a highly parallel and unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized, diagnostic mutant collection that is predictive all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode sequencing protocol, enabling assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened 7 different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.
GMPR: A novel normalization method for microbiome sequencing data
Authors: Chen Li , Chen Jun
Published: March 2017

Normalization is the first and a critical step in microbiome sequencing (microbiome-Seq) data analysis to account for variable library sizes. Though RNA-Seq based normalization methods have been adapted for microbiome-Seq data, they fail to consider the unique characteristics of microbiome-Seq data, which contain a vast number of zeros due to the physical absence or undersampling of the microbes. Normalization methods that specifically address the zeroinflation remain largely undeveloped. Here we propose GMPR - a simple but effective normalization method - for zeroinflated sequencing data such as microbiome-Seq data. Simulation studies and analyses of 38 real gut microbiome datasets from 16S rRNA gene amplicon sequencing demonstrated the superior performance of the proposed method.

Availability and Implementation

‘GMPR’ is implemented in R andavailable athttps://github.com/jchen1981/GMPR

Supplementary Information

Supplementary data are available at Bioinformatics online.

Contact

Chen.Jun2@mayo.edu
Genome-wide analysis of differential RNA editing in epilepsy
Authors: Srivastava Prashant Kumar , Bagnati Marta , Delahaye-Duriez Andree , Ko Jeong-Hun , Rotival Maxime , Langley Sarah R. , Shkura Kirill , Mazzuferi Manuela , Danis Bénédicte , van Eyll Jonathan , Foerch Patrik , Behmoaras Jacques , Kaminski Rafal M. , Petretto Enrico , Johnson Michael R.
Published: March 2017

The recoding of genetic information through RNA editing contributes to proteomic diversity, but the extent and significance of RNA editing in disease is poorly understood. In particular, few studies have investigated the relationship between RNA editing and disease at a genome-wide level. Here, we developed a framework for the genome-wide detection of RNA sites that are differentially edited in disease. Using RNA-sequencing data from 100 hippocampi from mice with epilepsy (pilocarpine–temporal lobe epilepsy model) and 100 healthy control hippocampi, we identified 256 RNA sites (overlapping with 87 genes) that were significantly differentially edited between epileptic cases and controls. The degree of differential RNA editing in epileptic mice correlated with frequency of seizures, and the set of genes differentially RNA-edited between case and control mice were enriched for functional terms highly relevant to epilepsy, including “neuron projection” and “seizures.” Genes with differential RNA editing were preferentially enriched for genes with a genetic association to epilepsy. Indeed, we found that they are significantly enriched for genes that harbor nonsynonymous de novo mutations in patients with epileptic encephalopathy and for common susceptibility variants associated with generalized epilepsy. These analyses reveal a functional convergence between genes that are differentially RNA-edited in acquired symptomatic epilepsy and those that contribute risk for genetic epilepsy. Taken together, our results suggest a potential role for RNA editing in the epileptic hippocampus in the occurrence and severity of epileptic seizures.
Mouse Ovary Transplantation
Authors: Behringer Richard
Published: March 2017

Ovary transplantation is a useful technique when there is a valuable female mouse (e.g., transgenic, unique allele) that is ill, not breeding, or cannot breed naturally. The ovaries from the valuable female are transplanted into a histocompatible wild-type female recipient whose ovaries have been surgically removed. The donor ovaries can then function in the wild-type recipient to generate oocytes that will be ovulated and can be fertilized after natural matings. The donor ovaries can be cut into smaller pieces and each piece can be transplanted into separate females. Newborn ovaries or cryorecovered ovaries can also be transplanted. The removal of the recipient ovary leaves the surrounding bursal membrane intact, providing a convenient sac to insert and hold the donor ovary or ovarian fragments.
Building Cell Structures in Three Dimensions: Electron Tomography Methods for Budding Yeast
Authors: O’Toole Eileen T. , Giddings Thomas H. , Winey Mark
Published: March 2017

Saccharomyces cerevisiae has been an important model system for numerous cellular, genetic, and molecular studies. However, this small eukaryote presents a challenge for imaging at the electron microscope level. Preparation of yeast using high-pressure freezing followed by freeze-substitution (HPF/FS) results in excellent preservation of cell structure in these difficult-to-fix samples. In particular, cells prepared by HPF/FS can be used for 3D electron tomography (ET) studies where optimum cell preservation is critical. Here, we discuss the advantages of using HPF/FS for ET and show examples of the utility of this method for building yeast cell structures in three dimensions.
Joint small-angle X-ray and neutron scattering data analysis of asymmetric lipid vesicles
Authors: Eicher Barbara , Heberle Frederick A. , Marquardt Drew , Rechberger Gerald N. , Katsaras John , Pabst Georg
Published: March 2017

Low- and high-resolution models describing the internal transbilayer structure of asymmetric lipid vesicles have been developed. These models can be used for the joint analysis of small-angle neutron and X-ray scattering data. The models describe the underlying scattering length density/electron density profiles either in terms of slabs or through the so-called scattering density profile, previously applied to symmetric lipid vesicles. Both models yield structural details of asymmetric membranes, such as the individual area per lipid, and the hydrocarbon thickness of the inner and outer bilayer leaflets. The scattering density profile model, however, comes at a cost of increased computational effort but results in greater structural resolution, showing a slightly lower packing of lipids in the outer bilayer leaflet of ∼120 nm diameter palmitoyloleoyl phosphatidylcholine (POPC) vesicles, compared to the inner leaflet. Analysis of asymmetric dipalmitoyl phosphatidylcholine/POPC vesicles did not reveal evidence of transbilayer coupling between the inner and outer leaflets at 323 K, i.e. above the melting transition temperature of the two lipids.
Nanoscale characterization of bismuth telluride epitaxial layers by advanced X-ray analysis
Authors: Morelhão Sérgio L. , Fornari Celso I. , Rappl Paulo H. O. , Abramof Eduardo
Published: March 2017

The surface properties of topological insulators are strongly correlated with their structural properties, requiring high-resolution techniques capable of probing both surface and bulk structures at once. In this work, the high flux of a synchrotron source, a set of recursive equations for fast X-ray dynamical diffraction simulation and a genetic algorithm for data fitting are combined to reveal the detailed structure of bismuth telluride epitaxial films with thicknesses ranging from 8 to 168 nm. This includes stacking sequences, thickness and composition of layers in model structures, interface coherence, surface termination, and morphology. The results are in agreement with the surface morphology determined by atomic force microscopy. Moreover, by using X-ray data from a zero-noise area detector to construct three-dimensional reciprocal-space maps, insights into the nanostructure of the domains and stacking faults in Bi2Te3 films are given.
New molecular packing in a crystal of pseudoazurin fromAlcaligenes faecalis: a double-helical arrangement of blue copper
Authors: Fukuda Yohta , Mizohata Eiichi , Inoue Tsuyoshi
Published: March 2017

Pseudoazurin from the denitrifying bacteriumAlcaligenes faecalis(AfPAz) is a blue copper protein and functions as an electron donor to copper-containing nitrite reductase (CuNIR). Conventionally,AfPAz has been crystallized using highly concentrated ammonium sulfate as a precipitant. Here, a needle-like crystal ofAfPAz grown in a solution containing a macromolecular precipitant, polyethylene glycol 8000 (PEG 8000), is reported. The crystal belonged to space groupP61, with unit-cell parametersa=b= 68.7,c= 94.2 Å. The structure has been determined and refined at 2.6 Å resolution. The asymmetric unit contained twoAfPAz molecules contacting each other on negatively charged surfaces. The molecular packing of the crystal showed a right-handed double-helical arrangement ofAfPAz molecules and hence of blue copper sites. This structure provides insight into the excluded-volume effect of PEG and the manner of assembly ofAfPAz.
Privacy-preserving recommendations in context-aware mobile environments
Authors: Polatidis Nikolaos , Georgiadis Christos K. , Pimenidis Elias , Stiakakis Emmanouil
Published: March 2017

Purpose

This paper aims to address privacy concerns that arise from the use of mobile recommender systems when processing contextual information relating to the user. Mobile recommender systems aim to solve the information overload problem by recommending products or services to users of Web services on mobile devices, such as smartphones or tablets, at any given point in time and in any possible location. They use recommendation methods, such as collaborative filtering or content-based filtering and use a considerable amount of contextual information to provide relevant recommendations. However, because of privacy concerns, users are not willing to provide the required personal information that would allow their views to be recorded and make these systems usable.

Design/methodology/approach

This work is focused on user privacy by providing a method for context privacy-preservation and privacy protection at user interface level. Thus, a set of algorithms that are part of the method has been designed with privacy protection in mind, which is done by using realistic dummy parameter creation. To demonstrate the applicability of the method, a relevant context-aware data set has been used to run performance and usability tests.

Findings

The proposed method has been experimentally evaluated using performance and usability evaluation tests and is shown that with a small decrease in terms of performance, user privacy can be protected.

Originality/value

This is a novel research paper that proposed a method for protecting the privacy of mobile recommender systems users when context parameters are used.
Does corporate ethics help investors forecast future earnings?
Authors: Lin Hsuan-Chu , Wang Chuan-San , Wu Ruei-Shian
Published: March 2017

Purpose

A firm’s ethical behavior is commonly perceived beneficial to the firm and its investors in the literature. However, activities of corporate social responsibility (CSR) are often delivered with multiple purposes, and their expenses are aggregated with other expenditures in financial statements. These two features motivate the authors to hypothesize and find that investors’ ability to predict future earnings of ethical firms may not be improved through observing the CSR activities. The study aims to suggest that CSR spending should be expressed separately from other expenses in financial reports to help investors predict the future performance of CSR firms.

Design/methodology/approach

The authors use future (forward) earnings response coefficients (FERC) to testing whether current stock returns reflect correct information about future earnings. The basic specification of FERC framework, initially developed by Collinset al.(1994), is a regression of current-year stock returns on past, concurrent and future reported earnings with future stock returns as a control variable. A significantly positive FERC provides evidence that investors have rich and correct information about future earnings.

Findings

The authors find less future earnings information contained in current stock returns for firms with higher intensity of CSR activities. The association is also negative between current stock returns and future earnings reported by firms with a higher degree of CSR spending aggregated with selling, general and administrative expenses (SG&A). In additional analyses, the intensity of CSR activities is positively associated the uncertainty of benefits, measured by the standard deviation of future earnings over the next five years. This future earnings variability does not exist, even though CSR spending is aggregated with SG&A, consistent with the basic principle that accounting expenses create no future economic impacts.

Originality/value

The authors contribute to the current debate over consequences of CSR activities and accounting for CSR spending from a different angle. A common belief is that voluntary disclosure on CSR activities would aid in reducing costs of equity capital and financial reporting errors. These studies provide corporate managers with good reasons and motivations to expect beneficial consequences of voluntary disclosure. The results show that general investors are less capable of predicting future earnings when there is a higher degree of CSR spending aggregated with SG&A. It also highlights potential problems in the disclosure of general-purpose financial reporting to accounting standard setters.
Promoting a strategic business focus to balance competitive advantage and corporate social responsibility – missing elements
Authors: Fish Alan J. , Wood Jack
Published: March 2017

Purpose

This paper aims to highlight dysfunctional multi-stakeholder relations and negative business outcomes, evidenced in lose/lose results, exacerbated by failure to acknowledge strategic business focus as a means to redress problematic business thinking and practice amongst key leadership teams associated with achieving balance between competitive advantage and corporate social responsibility.

Design/methodology/approach

The reframed strategic business focus has been developed using Eastern philosophy and Western organization theory and refers to four case examples of dysfunctional business thinking and practice.

Findings

Strategic business focus results from an interdependent and complementary positive mediating relationship between competitive advantage and corporate social responsibility, which is moderated by organization culture (organization core values, including shared value) and strategic human resource management (talent and mindset).

Research limitations/implications

Strategic business focus as proposed has not been empirically tested but seeks to address a conceptualization that competing business and stakeholder agendas are interdependent and complementary.

Practical implications

Strategic business focus seeks to redress traditional win/lose and lose/lose business outcomes, by supporting win/win results, represented by shared value amongst multi-stakeholders.

Social implications

Strategic business focus seeks to provide a means whereby corporate social responsibility, particularly the social contract, plays a key role in the decisions and practices of key leadership teams and the behaviour of corporate staff in host environments when seeking competitive advantage.

Originality/value

Eastern thinking and behaviour are usually undervalued in the western business literature, particularly in western business practice. Joint attention, however, may improve competitive advantage and corporate social responsibility agendas in support of diverse management practices, including shared value.
Microbial communities in soil chronosequences with distinct parent material: the effect of soil pH and litter quality
Authors: Alfaro Fernando D. , Manzano Marlene , Marquet Pablo A. , Gaxiola Aurora
Published: March 2017

During soil development, bacteria and fungi can be differentially affected by changes in soil biogeochemistry. Since the chemistry of parent material affects soil pH, nutrient availability, and indirectly litter quality, we hypothesize that parent material has an important influence on microbial community patterns during long‐term soil development.

In this paper, we tested for the effect of parent material, as well as, soil and litter properties upon microbial community patterns in three c. 20 000‐year‐old semi‐arid chronosequences developed on sedimentary and volcanic (i.e. Andesitic and Dacitic) soils in the Dry Puna of Bolivia. We evaluated microbial patterns by analysing the terminal restriction fragment length polymorphism from amplified bacterial 16S rRNA genes, and the fungal internal transcribed spacer region, and quantitative real‐time polymerase chain reaction.

Soil and litter characteristics differed significantly between the Sedimentary and volcanic chronosequences. In particular, soil pH was alkaline in all stages of the Sedimentary chronosequence; whereas it changed from alkaline to near neutral across stages in both volcanic chronosequences. Composition of bacterial communities changed across volcanic chronosequences, and this change was associated with a reduction in soil pH and increases in litter quality, whereas no differences were found in the Sedimentary chronosequence. Fungal community composition, in contrast, did not change across any chronosequence.

Relative microbial abundance, expressed as the fungal:bacterial ratio, declined across stages of the Sedimentary chronosequence in association with decreases in TC and TP, whereas in the Andesitic chronosequence decreases in fungal:bacterial ratios were related with increases in litter quality and declines in soil pH.

Synthesis. Our results show the importance of parent material in affecting bacterial and fungal communities during soil development. Further, in semi‐arid chronosequences, fungal:bacterial ratios tend to decline given that soil pH in young soils is rather alkaline. Our results also are consistent with the general framework that highlights the importance of above‐ground (i.e. litter quality) and below‐ground (i.e. soil properties) in affecting microbial relative abundance and community composition during soil development.
Policy Uncertainty from a Central Bank Perspective
Authors: McDermott C. John
Published: March 2017

In this article, I argue that a substantial portion of macroeconomic policy uncertainty derives from the external environment, which propagates into uncertainty about actual policy. I also illustrate elements of the Reserve Bank of New Zealand's monetary policy framework that aim to mitigate uncertainty, highlighting our clear objectives, regular decision‐making cycle and active communication strategy. Lastly, I leave researchers with two questions: What measures of uncertainty should be pre‐eminently important to policy‐makers? And how should policy‐makers respond to those measurements?
An Aquatic Decomposition Scoring Method to Potentially Predict the Postmortem Submersion Interval of Bodies Recovered from the North Sea
Authors: van Daalen Marjolijn A. , de Kat Dorothée S. , Oude Grotebevelsborg Bernice F.L. , de Leeuwe Roosje , Warnaar Jeroen , Oostra Roelof Jan , M Duijst‐Heesters Wilma L.J.
Published: March 2017

This study aimed to develop an aquatic decomposition scoring (ADS) method and investigated the predictive value of this method in estimating the postmortem submersion interval (PMSI) of bodies recovered from the North Sea. This method, consisting of an ADS item list and a pictorial reference atlas, showed a high interobserver agreement (Krippendorff's alpha ≥ 0.93) and hence proved to be valid. This scoring method was applied to data, collected from closed cases—cases in which the postmortal submersion interval (PMSI) was known—concerning bodies recovered from the North Sea from 1990 to 2013. Thirty‐eight cases met the inclusion criteria and were scored by quantifying the observed total aquatic decomposition score (TADS). Statistical analysis demonstrated that TADS accurately predicts the PMSI (p < 0.001), confirming that the decomposition process in the North Sea is strongly correlated to time.
Comparative analysis of the Monochamus alternatus immune system
Authors: Zhou Jiao , Yu Hai‐Ying , Zhang Wei , Ahmad Faheem , Hu Song‐Nian , Zhao Li‐Lin , Zou Zhen , Sun Jiang‐Hua
Published: March 2017

The pine sawyer beetle, Monochamus alternatus, is regarded as a notorious forest pest in Asia, vectoring an invasive pathogenic nematode, Bursaphelenchus xylophilus, which is known to cause pine wilt disease. However, little sequence information is available for this vector beetle. This hampered the research on its immune system. Based on the transcriptome of M. alternatus, we have identified and characterized 194 immunity‐related genes in M. alternatus, and compared them with homologues molecules from other species known to exhibit immune responses against invading microbes. The lower number of putative immunity‐related genes in M. alternatus were attributed to fewer C‐type lectin, serine protease (SP) and anti‐microbial peptide (AMP) genes. Phylogenetic analysis revealed that M. alternatus had a unique recognition gene, galectin3, orthologues of which were not identified in Tribolium castaneum, Drosophila melanogastor, Anopheles gambiae and Apis mellifera. This suggested a lineage‐specific gene evolution for coleopteran insects. Our study provides the comprehensive sequence resources of the immunity‐related genes of M. alternatus, presenting valuable information for better understanding of the molecular mechanism of innate immunity processes in M. alternatus against B. xylophilus.
Heavy Prenatal Alcohol Exposure is Related to Smaller Corpus Callosum in Newborn MRI Scans
Authors: Jacobson Sandra W. , Jacobson Joseph L. , Molteno Christopher D. , Warton Christopher M.R. , Wintermark Pia , Hoyme H. Eugene , De Jong Greetje , Taylor Paul , Warton Fleur , Lindinger Nadine M. , Carter R. Colin , Dodge Neil C. , Grant Ellen , Warfield Simon K. , Zöllei Lilla , van der Kouwe André J.W. , Meintjes Ernesta M.
Published: March 2017

Background

Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross‐sectional area of the corpus callosum (CC).

Methods

Forty‐three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom‐designed birdcage coil for infants, which increases signal‐to‐noise ratio almost 2‐fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi‐echo FLASH protocol adapted for newborns, and a knowledge‐based procedure was used to hand‐segment the neonatal brains.

Results

CC was disproportionately smaller in alcohol‐exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy.

Conclusions

Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol‐related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.
Two Brief Measures of Alcohol Use Produce Different Results: AUDIT‐C and Quick Drinking Screen
Authors: Letourneau Brian , Sobell Linda Carter , Sobell Mark B. , Agrawal Sangeeta , Gioia Christopher J.
Published: March 2017

Background

Several psychometrically sound measures of alcohol use have been developed to assess drinking. The Alcohol Use Disorders Identification Test (AUDIT) and its shorter counterpart the AUDIT‐C, which contains the first 3 AUDIT questions, were developed by the World Health Organization and have become the preferred brief measures for screening and evaluating problem severity. This study compared the first 3 questions on the AUDIT with another psychometrically sound brief measure of alcohol use, the Quick Drinking Screen (QDS).

Methods

Data were obtained from a randomized controlled trial of a mail‐based intervention promoting self‐change with 472 alcohol abusers (n = 280, no prior alcohol treatment; n = 192, prior alcohol treatment). Participants’ retrospective self‐reports of alcohol consumption were collected using the QDS and the 3 AUDIT‐C questions and compared. Although both measures contain similar questions (2 quantity‐frequency and 1 binge drinking), they differ in 2 important ways: (i) temporal interval over which data are collected, and (ii) formatting of response options (i.e., a continuous number vs. categorical).

Results

Intraclass correlations for drinking variables were moderate to moderately high. A repeated‐measures MANOVA using treatment condition and gender as variables revealed significant differences in absolute values between the 2 drinking measures with the QDS showing greater consumption on almost all variables. Participants’ numerical answers on the QDS were compared to their categorical answers to the similar alcohol use questions on the AUDIT‐C. The comparison revealed that participants’ answers on the AUDIT‐C were associated with extreme variability compared to their QDS answers. This variability suggests the AUDIT‐C would be unreliable as a quantitative measure of alcohol consumption.

Conclusions

The differences between the 3 alcohol use questions on the AUDIT‐C and the same questions on the QDS may reflect the imprecision of the AUDIT‐C's drinking response categories. Results suggest that the QDS can be used to identify risky drinking and to provide a more informative characterization of a drinker's alcohol consumption than that provided by the AUDIT‐C.
Smartphone use in dermatology for clinical photography and consultation: Current practice and the law
Authors: Abbott Lisa M , Magnusson Roger S , Gibbs Emma , Smith Saxon D
Published: March 2017

Background

Smartphones are rapidly changing the way doctors capture and communicate clinical information, particularly in highly visual specialties such as dermatology. An understanding of how and why smartphones are currently used in clinical practice is critical in order to evaluate professional and legal risks, and to formulate policies that enable safe use of mobile technologies for the maximal benefit of practitioners and patients.

Methods

Australian dermatologists and dermatology trainees were surveyed on their current practices relating to clinical smartphone use.

Results

Of the 105 respondents, 101 provided useable results. The data show clinical smartphone use is common and frequent, with more than 50% of respondents sending and receiving images on their smartphones at least weekly. Clinical photographs were usually sent via multimedia message or email and were commonly stored on smartphones (46%). Security measures adopted to protect data were limited. There was inadequate documentation of consent for transmission of photographs and advice provided. Only 22% of respondents were aware of clear policies in their workplace regarding smartphone use, and a majority desired further education on digital image management.

Conclusions

Given the frequency of use and the degree of importance placed on the ability to send and receive clinical images, clinical smartphone use will persist and will likely increase over time. Current practices are insufficient to comply with professional and legal obligations, and increase practitioners’ vulnerability to civil and disciplinary proceedings. Further education, realistic policies and adequate software resources are critical to ensure protection of patients, practitioners and the reputation of the dermatological profession.
Assessment of heart rate response to exercise and recovery during treadmill testing in arsenic‐exposed workers
Authors: Karakulak Ugur Nadir , Gunduzoz Meside , Ayturk Mehmet , Tek Ozturk Mujgan , Tutkun Engin , Yilmaz Omer Hinc
Published: March 2017

Background

Arsenic exposure is associated with various cardiovascular diseases. The aim of the present study was to assess cardiac autonomic function via heart rate response to exercise and recovery period of treadmill testing in arsenic‐exposed workers.

Methods

Sixty‐five (65) occupationally arsenic‐exposed workers and 35 healthy controls were enrolled. Blood and urinary arsenic levels were analyzed and symptom limited maximal treadmill exercise test were performed. Chronotropic response to exercise including age‐predicted maximal heart rate (APMHR), heart rate reserve (HRreserve), age‐predicted HRreserve (APHRreserve) and adjusted HRreserve and 1st‐, 2nd‐and 3rd‐min heart rate recovery (HRR) indices were calculated.

Results

Baseline clinical and echocardiographic parameters, exercise test duration, resting and maximal heart rate, peak exercise capacity, HRreserve, APMHR, APHRreserve, and adjusted HRreserve were found to be similar between groups. HRR1 (22.0 ± 4.3 vs. 24.3 ± 3.1 bpm, p = .003) and HRR2 (43.2 ± 6.2 vs. 46.7 ± 6.4 bpm, p = .012) were significantly lower in arsenic‐exposed workers compared to controls. Blood and urinary arsenic levels negatively correlated with HRR1 (r = −.477, p < .001 and r = −.438, p < .001, respectively) and HRR2 (r = −.507, p < .001 and r = −.412, p < .001 respectively).

Conclusions

Arsenic‐exposed workers had lower HRR indices than normal subjects but chronotropic response were similar. Cardiac autonomic dysregulation may be one of the cardiovascular consequences of arsenic exposure.
Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis
Authors: Allen P. B. , Olivera P. , Emery P. , Moulin D. , Jouzeau J.‐Y. , Netter P. , Danese S. , Feagan B. , Sandborn W. J. , Peyrin‐Biroulet L.
Published: March 2017

Background

Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability.

Aim

To review the similarities and differences in treatment goals between CD and rheumatoid arthritis.

Methods

This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis.

Results

Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat‐to‐target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease‐modification trials in CD.

Conclusions

Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients’ lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease‐modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease‐modification trials in CD in the near future.
Inflammatory cytokines compromise programmed cell death-1 (PD-1)-mediated T cell suppression in inflammatory arthritis through up-regulation of soluble PD-1
Authors: Bommarito D , Hall C , Taams L S , Corrigall V M
Published: March 2017

The programmed cell death 1 (PD-1) receptor plays a major role in regulating T cell activation. Our aim was to determine how inflammation influences PD-1-mediated T cell suppression. Flow cytometry analysis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovial fluid (SF) mononuclear cells showed an increase in the percentage of PD-1+ cells within the CD4+ and CD8+ T cell compartment compared to paired peripheral blood (PB). Upon in-vitro T cell receptor (TCR) stimulation of healthy control (HC) CD4+ T cells in the presence of plate-bound PD-L1fc chimera, significantly decreased proliferation and interferon (IFN)-γ secretion was observed. In contrast, CD4+ T cells from RA and PsA PB and SF appeared resistant to such PD-1-mediated inhibition. Addition of the proinflammatory cytokines tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-1β, which were increased in RA and PsA SF compared to osteoarthritis (OA) SF, consistently abrogated PD-1-mediated suppression in HC CD4+ T cell cultures. This effect was reversed by inhibitors of these cytokines. Soluble PD-1 (sPD-1) levels were increased in cell culture supernatants from TNFα and IL-6-stimulated cultures compared to untreated controls, and also in RA and PsA, but not in OA, serum and SF. Functionally, addition of sPD-1fc counteracted PD-1-mediated suppression of HC CD4+ T cells, and increased T cell proliferation in HC CD4+ T cell/monocyte co-cultures. These in-vitro findings indicate that CD4+ T cells from patients with RA and PsA show increased resistance to PD-1-mediated suppression, which may be explained in part by the presence of soluble PD-1 in the inflammatory environment.
Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization
Authors: Martínez Rosa , Gutierrez‐Nogués Ángel , Fernández‐Ramos Concepción , Velayos Teresa , Vela Amaia ,   Spanish Congenital Hyperinsulinism Group, Navas María‐Ángeles , Castaño Luis
Published: March 2017

Background

Mutations in the GCK gene lead to different forms of glucokinase (GCK)‐disease, activating mutations cause hyperinsulinaemic hypoglycaemia while inactivating mutations cause monogenic diabetes. Hyperinsulinism (HI) is a heterogeneous condition with a significant genetic component. The major causes are channelopathies, the other forms are rare and being caused by mutations in genes such as GCK.

Objective

To describe the clinical and genetic presentation of four families with activating GCK mutations, and to explore the pathogenicity of the novel mutation identified through functional studies.

Results

Four cases of HI with mutations in GCK were identified. These include one novel mutation (p.Trp99Cys). Functional analysis of the purified mutant fusion protein glutathione‐S‐transferase (GST)‐GCK‐p.Trp99Cys demonstrated that p.Trp99Cys is an activating mutation as it induces a higher affinity for glucose and increases the relative activity index more than 11 times. Moreover, the thermal stability of the mutant protein was similar to that of its wild type. All patients were responsive to diazoxide treatment. One of the mutations arose de novo, and two were dominantly inherited, although only one of them from an HI affected parent. The age of presentation in our cases varied widely from the neonatal period to adulthood.

Conclusion

The clinical phenotype of the GCK activating mutation carriers was heterogeneous, the severity of symptoms and age at presentation varied markedly between affected individuals, even within the same family. The novel activating GCK mutation (p.Trp99Cys) has a strong activating effect in vitro although it has been identified in one case of a milder and late‐onset form of HI.
Molecular phylogeny of Glossodoris (Ehrenberg, 1831) nudibranchs and related genera reveals cryptic and pseudocryptic species complexes
Authors: Matsuda Shayle B. , Gosliner Terrence M.
Published: March 2017

Chromodorid nudibranchs (Chromodorididae) are brightly coloured sea slugs that live in some of the most biodiverse and threatened coral reefs on the planet. However, the evolutionary relationships within this family have not been well understood, especially in the genus Glossodoris. Members of Glossodoris have experienced large‐scale taxonomic instability over the last century and have been the subject of repeated taxonomic changes, in part due to morphological characters being the sole traditional taxonomic sources of data. Changing concepts of traditional generic boundaries based on morphology also have contributed to this instability. Despite recent advances in molecular systematics, many aspects of chromodorid taxonomy remain poorly understood, particularly at the traditional species and generic levels. In this study, 77 individuals comprising 32 previously defined species were used to build the most robust phylogenetic tree of Glossodoris and related genera using mitochondrial genes cytochrome c oxidase subunit I and 16S, and the nuclear gene 28S. Bayesian inference, maximum likelihood, and maximum parsimony analyses verify the most recent hypothesized evolutionary relationships within Glossodoris. Additionally, a pseudocryptic and cryptic species complex within Glossodoris cincta and a pseudocryptic complex within Glossodoris pallida emerged, and three new species of Doriprismatica are identified.