bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements on microwave-to-optics conversion device for quantum information networks
Authors: Kim Meeri
Published: September 2017

A new design for an electro-optomechanical device uses a microwave 3D cavity and wireless coupling to improve performance.
New study models diffusion of hazardous fission products through protective barriers
Authors: Kim Meeri
Published: September 2017

Researchers from the University of Wisconsin-Madison investigate how cesium isotopes diffuse through a barrier of silicon carbide.
Row spacing is more important than seeding rate for increasing Rhodes grass (Chloris gayana) control and grain yield in soybean (Glycine max)
Authors: Rasool Ghulam , Mahajan Gulshan , Yadav Rajpaul , Hanif Zarka , Chauhan Bhagirath Singh
Published: September 2017

In Australia, soybean (Glycine max (L.) Merr.) is planted at a low density in wide rows, and weeds substantially reduce yield because of opportunities for their growth in the wide rows. Field studies were conducted over 2 years at the University of Queensland farm, Gatton, Australia, to assess the effect of row spacing and seeding rate on the competitiveness of soybeans with a model weed, Rhodes grass (Chloris gayana Kunth). The experiment was conducted in a split-split plot design, replicated three times. Main plots comprised two seeding rates (40 and 80 kg ha–1), subplots two row spacings (25 and 75 cm), and sub-subplots four Rhodes grass infestation periods (weedy from planting to maturity, weedy from 3 weeks after planting (WAP) to maturity, weedy from 6 WAP to maturity, and weed-free from planting to maturity). The results showed that seed rate did not influence Rhodes grass biomass or soybean yield. Soybean yield was greater and Rhodes grass biomass was less in the 25-cm rows than the 75-cm rows. For the 25-cm rows, Rhodes grass biomass in the plots infested beyond 3 WAP was 81–89% less than in the season-long weedy plots, whereas for the wider row crop, this reduction was only 60–75%. For the 25-cm rows, soybean yield in the plots infested with Rhodes grass beyond 3 WAP was 30–36% less than under weed-free condition. However, for the 75-cm rows, this reduction was 56–65%. The results suggest that planting soybean in wider rows caused greater reduction in yield and required an earlier weed management program than planting in narrow rows. The study also suggested that narrowing row spacing was more important than increasing seeding rates for improving weed control and soybean grain yield.
The on-site quality-assurance system for Hyper Suprime-Cam: OSQAH
Authors: Furusawa Hisanori , Koike Michitaro , Takata Tadafumi , Okura Yuki , Miyatake Hironao , Lupton Robert H , Bickerton Steven , Price Paul A , Bosch James , Yasuda Naoki , Mineo Sogo , Yamada Yoshihiko , Miyazaki Satoshi , Nakata Fumiaki , Koshida Shintaro , Komiyama Yutaka , Utsumi Yousuke , Kawanomoto Satoshi , Jeschke Eric , Noumaru Junichi , Schubert Kiaina , Iwata Ikuru , Finet Francois , Fujiyoshi Takuya , Tajitsu Akito , Terai Tsuyoshi , Lee Chien-Hsiu
Published: September 2017

We have developed an automated quick data analysis system for data quality assurance (QA) for Hyper Suprime-Cam (HSC). The system was commissioned in 2012–2014, and has been offered for general observations, including the HSC Subaru Strategic Program, since 2014 March. The system provides observers with data quality information, such as seeing, sky background level, and sky transparency, based on quick analysis as data are acquired. Quick-look images and validation of image focus are also provided through an interactive web application. The system is responsible for the automatic extraction of QA information from acquired raw data into a database, to assist with observation planning, assess progress of all observing programs, and monitor long-term efficiency variations of the instrument and telescope. Enhancements of the system are being planned to facilitate final data analysis, to improve the HSC archive, and to provide legacy products for astronomical communities.
Operative Stabilization of Flail Chest Injuries Reduces Mortality to That of Stable Chest Wall Injuries
Authors: Dehghan Niloofar , Mah Jeffrey M. , Schemitsch Emil H. , Nauth Aaron , Vicente Milena , McKee Michael D.
Published: September 2017

Objective:

To determine the prevalence, management and outcomes of patients with flail chest injuries, compared to patients without flail chest injuries (single rib fractures and multiple rib fractures without a flail segment).

Design:

Retrospective cohort study.

Setting:

Ontario, Canada.

Participants:

Ontario residents over the age of 16 years who had been admitted to hospital with a chest wall injury from 2004 to 2015 were identified using administrative health care databases.

Main Outcome Measurements:

Outcomes included treatment modalities such as rate of surgical repair, days on mechanical ventilation, days in the intensive care unit, days in hospital, rate of chest tube placement; and rates of complication, including pneumonia, tracheostomy, readmission, and death.

Results:

In total 117,204 patients with fractures of the chest wall were identified. Of the entire cohort, 1.5% of them had a flail chest injury, 41% had multiple rib fractures, and 58% had single rib fractures. Patients with flail chest injuries had significantly worse outcomes compared to patients with multiple rib fractures in all categories (P < 0.0001). Similarly, patients with multiple rib fractures had significantly worst outcomes compared with patients with single rib fractures (P < 0.0001). Only 4.5% of patients with flail chest injuries were treated surgically, however, the number increased from 1% before 2010 to 10% after 2010 (P < 0.0001). After adjustment for potential confounders, patients with flail chest injuries treated surgically had a reduced risk of early mortality compared to those treated nonoperatively (OR 0.16, P = 0.019).

Conclusions:

Surgical stabilization of flail chest injuries has increased significantly in recent years. The results of this study provide preliminary evidence that the increasing rate of surgical intervention may be warranted by reducing mortality.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Faith and Ethics, Covenant and Code
Authors: Fowler Marsha D.
Published: September 2017

How does and should the American Nurses Association Code of Ethics for Nurses with Interpretive Statements, with foundations from the late 1800s, impact today's nursing practice? How can the Code help you? The earlier 2001 Code was revised and became effective January 2015. The nine provisions received modest revision, as did the corresponding interpretive statements. However, Provisions 8 and 9 and their interpretive statements received more substantial revision. This article explains the Code and summarizes the 2015 revisions, considering points of particular interest for nurses of faith.
Design and Psychometric Evaluation of the Quality of Life in Patients With Anal Fistula Questionnaire
Authors: Ferrer-Márquez Manuel , Espínola-Cortés Natalia , Reina-Duarte Angel , Granero-Molina José , Fernández-Sola Cayetano , Hernández-Padilla José Manuel
Published: September 2017

BACKGROUND:

Quality of life is often considered when deciding and evaluating the treatment strategy for patients diagnosed with anal fistula.

OBJECTIVE:

The purpose of this study was to develop and psychometrically test the Quality of Life in Patients with Anal Fistula Questionnaire.

DESIGN:

This was an observational cross-sectional study for the development and validation of a psychometric tool.

SETTINGS:

The study was conducted at a general hospital in the southeast of Spain.

PATIENTS:

A convenience sample included 54 patients diagnosed with anal fistula.

MAIN OUTCOMES MEASURES:

The reliability of the tool was assessed through its internal consistency (Cronbach α) and temporal stability (Spearman correlation coefficient (r) between test–retest). The content validity index of the items and the scale was calculated. Correlation analysis and an ordinal regression analysis between the developed tool and the Short Form 12 Health Survey examined its concurrent validity. Principal component analysis and known-group analysis using the Kruskal–Wallis test examined its construct validity.

RESULTS:

The reliability of the developed questionnaire was very high (α = 0.908; r = 0.861; p < 0.01). Its content validity was excellent (all-item content validity index = 0.79–1.00; scale validity index = 0.92). Evidence of its concurrent validity included strong correlation between the developed tool and Short Form 12 Health Survey (r = 0.734; p < 0.001), and participant scores on the developed tool explained ≈46.2% of the between-subject variation for the participant scores on Short Form 12 Health Survey (Nagelkerke R
2 = 0.462). Confirming its construct validity, principal component analysis revealed that 2 factors explained 81.63% of the total variance found. Known-group analysis evidenced the ability of the questionnaire to detect expected differences in patients presenting with different symptomatology.

LIMITATIONS:

The major limitations of this study were the use of a small sample of Spanish-speaking patients, not including patients in the initial development of the questionnaire, and developing the scoring system using a summation method.

CONCLUSIONS:

The Quality of Life in Patients with Anal Fistula Questionnaire has proven to be a valid, reliable, and concise tool that could contribute to the evaluation of quality of life among patients with an anal fistula. See Video Abstract at http://links.lww.com/DCR/A368.
Sphincter-Sparing Anal Fistula Repair: Are We Getting Better?
Authors: Sugrue Jeremy , Mantilla Nathalie , Abcarian Ariane , Kochar Kunal , Marecik Slawomir , Chaudhry Vivek , Mellgren Anders , Nordenstam Johan
Published: September 2017

BACKGROUND:

Sphincter-sparing repairs are commonly used to treat anal fistulas with significant muscle involvement.

OBJECTIVE:

The current study evaluates the trends and efficacy of sphincter-sparing repairs and determines risk factors for fistula recurrence.

DESIGN AND SETTINGS:

A retrospective review was performed at 3 university-affiliated teaching hospitals.

PATIENTS:

All 462 patients with cryptoglandular anal fistulas who underwent 573 sphincter-sparing repairs between 2005 and 2015 were included. Patients with Crohn’s disease were excluded.

MAIN OUTCOME MEASURES:

The primary outcome was the rate of fistula healing defined as cessation of drainage with closure of the external opening. Risk factors for nonhealing were also analyzed.

RESULTS:

Five hundred three sphincter-sparing repairs were analyzed, whereas 70 were lost to follow-up. Two hundred twenty sphincter-sparing repairs (44%) resulted in healing, 283 (56%) resulted in nonhealing with a median follow-up of 9 (range, 1–125) months. The median time to fistula recurrence was 3 (range, 0–75) months with 79% and 91% of recurrences noted within 6 and 12 months. Patients treated with a dermal advancement flap, rectal advancement flap, or ligation of the intersphincteric tract procedure were less likely to have a recurrence than patients treated with a fistula plug or fibrin glue (p < 0.001). Over time, there was a significantly increased use of the ligation of the intersphincteric tract procedure (p < 0.001) and a significantly decreased use of fistula plugs and fibrin glue (p < 0.001); healing rates improved accordingly. There were no significant differences in healing rates with respect to patient demographics, comorbidities, or fistula characteristics.

LIMITATIONS:

This study was limited by its retrospective design.

CONCLUSIONS:

Healing rates following sphincter-sparing repairs of cryptoglandular anal fistulas are modest, but have improved over time with the use of better surgical techniques. In this study, ligation of the intersphincteric fistula tract and flaps were superior to fistula plugs and fibrin glue; the former procedures are therefore favored. See Video Abstract at http://links.lww.com/DCR/A391.
Ocular Demodicosis as a Potential Cause of Ocular Surface Inflammation
Authors: Luo Xiaohui , Li Jing , Chen Chuan , Tseng Scheffer , Liang Lingyi
Published: September 2017

Among different species of mites, Demodex folliculorum and Demodex brevis are the only 2 that affect the human eye. Because demodicosis is highly age-dependent and can be found in asymptomatic adults, the pathogenicity of these mites has long been debated. In this study, we summarize our research experience including our most recent study regarding Demodex infestation as a potential cause of ocular inflammatory diseases. Specifically, we describe the pathogenesis of demodicosis and then discuss the results of work investigating the associations and relationships between ocular demodicosis and blepharitis, meibomian gland diseases, and keratitis, in turn. This is followed by some discussion of the diagnosis of demodicosis and concludes with a brief discussion of evidence for different treatments for ocular demodicosis. Collectively, our studies suggest a strong correlation between ocular demodicosis and ocular surface inflammatory conditions, such as blepharitis, chalazia, meibomian gland dysfunction, and keratitis. Further investigation of the underlying pathogenic mechanism is warranted.
Compliance With Hand-Washing Guidelines Among Visitors From the Community to Acute Care Settings: A Scoping Review
Authors: Compton Dinah , Davenport Todd E.
Published: September 2017

Background:

Health care–associated infections are widely acknowledged to be an important public health issue. Hand hygiene guidelines for health care workers are common, but remain uncommon for visitors.

Purpose:

The purpose of this systematic review is to examine the methodological quality of articles indicating the adherence and efficacy of hand hygiene compliance of community visitors to the acute care setting.

Data Sources:

Academic Search Complete, CINAHL, Cochrane Library, Medline, and PubMedß.

Study Selection:

A systematic literature search was conducted for articles describing hand-washing efficacy among visitors in an acute care setting using the following Medical Subject Headings (MeSH) terms: “clinical trial,” “evaluation studies,” “randomized controlled trial,” “cross infection/epidemiology,” “cross infection/prevention & control,” “hand disinfection/standards,” “intervention studies,” “guideline adherence/statistics & numerical data,” “risk factors,” “skin care/standards,” and “time factors.” Primary or secondary research studies that were published in peer-reviewed journals, written in English, and involving hospital visitor hand hygiene compliance were included. The Downs and Black (D&B) checklist was used to document the methodological quality. The Cochrane Collaborative checklist was used to assess the risk of bias.

Data Synthesis:

Mean D&B scores were 17/27. Baseline hand hygiene compliance for visitors was 0.5% to 11% at the hospital main entrance, 9% to 35% for general and surgical units, 11% for isolation rooms, 39% in pediatric wards, 3.95% to 49.1% at bedside, and 7% to 94% for intensive care units. Posted signs, de-germer dispensers, and pandemic influenza status all increased hand hygiene compliance over baseline observations.

Limitations:

Studies were generally low quality and at high risk for bias. In addition, data could not be pooled. This was attributed to the unavailability of prospective controlled trials. Substantial heterogeneity was found in the number and types of dependent variable measures.

Conclusions:

Visitor compliance with hand hygiene guidelines is highly variable but may be amenable to public health interventions. Higher quality studies focused on health outcomes are necessary to generate best practice recommendations related to hand hygiene.
Nodular Lymphocyte-predominant Hodgkin Lymphoma in a 15-Year-Old Boy With Li-Fraumeni Syndrome Having a Germline TP53 D49H Mutation
Authors: Yamazaki Fumito , Shima Haruko , Osumi Tomoo , Narumi Satoshi , Kuroda Tatsuo , Shimada Hiroyuki
Published: September 2017

Germline mutations in TP53 are the primary cause of Li-Fraumeni syndrome (LFS). Most mutations are reported within the DNA-binding domain. We report a case of a 15-year-old boy with LFS who developed early-stage nodular lymphocyte-predominant Hodgkin lymphoma, a rare subtype of Hodgkin lymphomas. His sister was diagnosed with embryonal rhabdomyosarcoma at the age of 1.5 years. Sequence analysis revealed a germline mutation in the transactivation domain of TP53, c.145G>C (p.D49H), in the patient, his sister, and father. One family with LFS with a germline TP53 D49H mutation has previously been reported. This report supports the pathogenicity of this mutation.
Contrast-enhanced 3-dimensional Fluid-attenuated Inversion Recovery Sequences Have Greater Sensitivity for Detection of Leptomeningeal Metastases in Pediatric Brain Tumors Compared With Conventional Spoiled Gradient Echo Sequences
Authors: Utz Michael J. , Tamber Mandeep S. , Mason Gary E. , Pollack Ian F. , Panigrahy Ashok , Zuccoli Giulio
Published: September 2017

Postcontrast 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences have reduced vascular and flow-related artifacts and high sensitivity to low gadolinium concentrations. We compared the performance of postcontrast spoiled gradient echo images to 3D-FLAIR in the detection of leptomeningeal metastases in 47 pediatric patients with brain tumors. We found 10 cases with more leptomeningeal signal abnormalities on 3D-FLAIR. Overall there were significantly more lesions on 3D-FLAIR than spoiled gradient echo sequences. We believe the increased detection of leptomeningeal signal abnormality is due to increased sensitivity for low concentrations of gadolinium in regions of early blood brain barrier breakdown. Our study was limited by the lack of leptomeningeal metastases in cerebrospinal fluid sampling. We plan to conduct future studies which will determine whether the time-based concentration of gadolinium affects the performance and results. Future studies will also require more cases of pathology-proven leptomeningeal disease.
A Comparison of Error Rates Between Intravenous Push Methods: A Prospective, Multisite, Observational Study
Authors: Hertig John B. , Degnan Daniel D. , Scott Catherine R. , Lenz Janelle R. , Li Xiaochun , Anderson Chelsea M.
Published: September 2017

Objectives

Current literature estimates the error rate associated with the preparation and administration of all intravenous (IV) medications to be 9.4% to 97.7% worldwide. This study aims to compare the number of observed medication preparation and administration errors between the only commercially available ready-to-administer product (Simplist) and IV push traditional practice, including a cartridge-based syringe system (Carpuject) and vials and syringes.

Methods

A prospective, multisite, observational study was conducted in 3 health systems in various states within the United States between December 2015 and March 2016 to observe IV push medication preparation and administration. Researchers observed a ready-to-administer product and IV push traditional practice using a validated observational method and a modified data collection sheet. All observations were reconciled to the original medication order to determine if any errors occurred.

Results

Researchers collected 329 observations (ready to administer = 102; traditional practice = 227) and observed 260 errors (ready to administer = 25; traditional practice = 235). The overall observed error rate for ready-to-administer products was 2.5%, and the observed error rate for IV push traditional practice was 10.4%.

Conclusions

The ready-to-administer group demonstrated a statistically significant lower observed error rate, suggesting that use of this product is associated with fewer observed preparation and administration errors in the clinical setting. Future studies should be completed to determine the potential for patient harm associated with these errors and improve clinical practice because it relates to the safe administration of IV push medications.
Polysaccharide-mediated synthesis of melanins from serotonin and other 5-hydroxy indoles
Authors: Vercruysse Koen , Clark Astiney , Alatas Noor , Brooks Dylan , Hamza Nafisa , Whalen Margaret
Published: September 2017

As a continuation of our research on the melanin formation from catecholamines, we studied the polysaccharide-mediated oxidation of serotonin and other 5-hydroxy indoles into melanin-like materials. As for the catecholamines, we observed that many polysaccharides promote the oxidation of such compounds, particularly in the presence of Cu2+. The reactions were monitored using RP-HPLC and SEC techniques. Melanin-like materials were purified through dialysis and evaluated using UV_Vis and FT_IR spectroscopic techniques. One such material, synthesized from chondroitin sulfate type A and serotonin in the presence of Cu2+was found to affect the release of IL-lβ and IL-6 cytokines from immune cells.
The Impact of In-Scanner Head Motion on Structural Connectivity Derived from Diffusion Tensor Imaging
Authors: Baum Graham L. , Roalf David R. , Cook Philip A. , Ciric Rastko , Rosen Adon F.G. , Xia Cedric , Elliot Mark A. , Ruparel Kosha , Verma Ragini , Tunc Birkan , Gur Ruben C. , Gur Raquel E. , Bassett Danielle S. , Satterthwaite Theodore D.
Published: September 2017

Multiple studies have shown that data quality is a critical confound in the construction of brain networks derived from functional MRI. This problem is particularly relevant for studies of human brain development where important variables (such as participant age) are correlated with data quality. Nevertheless, the impact of head motion on estimates of structural connectivity derived from diffusion tractography methods remains poorly characterized. Here, we evaluated the impact of in-scanner head motion on structural connectivity using a sample of 949 participants (ages 8-23 years old) who passed a rigorous quality assessment protocol for diffusion tensor imaging (DTI) acquired as part of the Philadelphia Neurodevelopmental Cohort. Structural brain networks were constructed for each participant using both deterministic and probabilistic tractography. We hypothesized that subtle variation in head motion would systematically bias estimates of structural connectivity and confound developmental inference, as observed in previous studies of functional connectivity. Even following quality assurance and retrospective correction for head motion, eddy currents, and field distortions, in-scanner head motion significantly impacted the strength of structural connectivity in a consistency-and length-dependent manner. Specifically, increased head motion was associated with reduced estimates of structural connectivity for high-consistency network edges, which included both short-and long-range connections. In contrast, motion inflated estimates of structural connectivity for low-consistency network edges that were primarily shorter-range. Finally, we demonstrate that age-related differences in head motion can both inflate and obscure developmental inferences on structural connectivity. Taken together, these data delineate the systematic impact of head motion on structural connectivity, and provide a critical context for identifying motion-related confounds in studies of structural brain network development.
Genome-Wide Association Studies Identify 15 Genetic Markers Associated with Marmite Taste Preference
Authors: Roos Thomas R. , A. Kulemin Nikolay , I. Ahmetov Ildus , Lasarow Avi , Grimaldi Keith
Published: September 2017

Marmite is a popular food eaten around the world, to which individuals have commonly considered themselves either “lovers” or “haters”. We aimed to determine whether this food preference has a genetic basis.Weperformed a genome-wide association study (GWAS) for Marmite taste preference using genotype and questionnaire data froma cohort of 261 healthy adults. We found 1 single nucleotide polymorphism (SNP) associated with Marmite taste preferencethat reached genome-wide significance (p<5x10-8) in our GWAS analyses. We found another 4 SNPsassociated with Marmite taste preference that reached genome-wide significance (p<5x10-8) in at leastoneGWAS and/or for at least one phenotype analysed. Moreover, we identified 10 additional SNPs potentially associated with Marmite taste preference through candidate gene analysis. Our results indicate that there is a genetic basis to Marmite taste preference and we have identified 15 genetic markers for this trait. Overall, we conclude that Marmite tastepreference is a complex human trait influenced by multiple genetic markers, as well as the environment.

Summary of Main Results

Marmite taste preference is a complex human trait with many factors influencing whether an individual loves or hates Marmite.

The relative contribution of genetics versus environment (ie. heritability) for Marmite taste preference is unknown.

The genetic contribution to Marmite taste preference involves multiple genetic markers each contributing a small amount (ie. the trait is polygenic). There is not one single Marmite gene with a large contribution like in thecase of theTAS2R38gene and bitter taste perception.

We have found a total of 15 SNPs associated with Marmite taste preference: 5 SNPs by a genetic-association screen atgenome-wide significance, and 10 SNPs by a candidate gene approach at nominal significance.

We did not find an association between theTAS2R38bitter taste receptor gene and Marmite taste preference.

It is important to independently replicate the findings of this study in order to validate these genetic markers and get a more accurate idea of their true effect on Marmite taste preference.
Complex Models of Sequence Evolution Require Accurate Estimators as Exemplified with the Invariable Site plus Gamma Model
Authors: Nguyen Lam-Tung , von Haeseler Arndt , Quang Minh Bui
Published: September 2017

The invariable site plus Γ model is widely used to model rate heterogeneity among alignment sites in maximum likelihood and Bayesian phylogenetic analyses. The proof that the invariable site plus continuous Γ model is identifiable (model parameters can be inferred correctly given enough data) has increased the creditability of its application to phylogeny reconstruction. However, most phylogenetic software implement the invariable site plus discrete Γ model, whose identifiability is likely but unproven. How well the parameters of the invariable site plus discrete Γ model are estimated is still disputed. Especially the correlation of the fraction of invariable sites with the fractions of sites with a slow evolutionary rate is discussed as being problematic. We show that optimization heuristics as implemented in frequently used phylogenetic software cannot always reliably estimate the shape parameter, the proportion of invariable sites and the tree length. Here, we propose an improved optimization heuristic that accurately estimates the three parameters. While research efforts mainly focus on tree search methods, our results signify the equal importance of verifying and developing effective estimation methods for complex models of sequence evolution.
A sequence-based, deep learning model accurately predicts RNA splicing branchpoints
Authors: Paggi Joseph M. , Bejerano Gill
Published: September 2017

Experimental detection of RNA splicing branchpoints, the nucleotide serving as the nucleophile in the first catalytic step of splicing, is difficult. To date, annotations exist for only 16-21% of 3’ splice sites in the human genome and even these limited annotations have been shown to be plagued by noise. We develop a sequence-only, deep learning based branchpoint predictor, LaBranchoR, which we conclude predicts a correct branchpoint for over 90% of 3’ splice sites genome-wide. Our predicted branchpoints show large agreement with trends observed in the raw data, but analysis of conservation signatures and overlap with pathogenic variants reveal that our predicted branchpoints are generally more reliable than the raw data itself. We use our predicted branchpoints to identify a sequence element upstream of branchpoints consistent with extended U2 snRNA base pairing, show an association between weak branchpoints and alternative splicing, and explore the effects of variants on branchpoints.
Hsf1 phosphorylation generates cell-to-cell variation in Hsp90 levels and promotes phenotypic plasticity
Authors: Zheng Xu , Beyzavi Ali , Krakowiak Joanna , Patel Nikit , Khalil Ahmad S. , Pincus David
Published: September 2017

Clonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this “noise” in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock transcription factor (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90 – a known “phenotypic capacitor” and canonical Hsf1 target. We show that Hsf1 phosphorylation promotes cell-to-cell variation, and this variation – rather than absolute Hsf1 activity – promotes antifungal resistance. We propose that Hsf1 phosphorylation enables differential tuning of the proteostasis network in individual cells, allowing populations to access a wide range of phenotypic states.
Basolateral amygdala glutamatergic neurons maintain aversive emotional salience
Authors: Sengupta Auntora , Yau Joanna O.Y. , Bressel Philip Jean-Richard Dit , Liu Yu , Zayra Millan E. , Power John M. , McNally Gavan P.
Published: September 2017

Basolateral amygdala (BLA) glutamatergic neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in rats. We show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of aversive reinforcement or non-reinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviours. This salience reduction was stimulus-specific, long-lasting, and specific to aversive emotional states - precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of BLA glutamatergic neurons is to maintain the salience of conditioned stimuli. This is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior.

Significance statement

The amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of reinforcement or non-reinforcement disrupts maintenance of conditioned stimulus (CS) salience. This causes a stimulus-specific, long-lasting, and aversive emotion specific deficit in the ability of the CS to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.
Canadian immigrant guidelines on how to become productive members of society
Authors: Krysa Isabella M. , Mills Albert , Barragan Salvador
Published: September 2017

Purpose

The purpose of this paper is to critically look at how immigrants to Canada are informed and educated about how to become productive members of society. The authors adopted a postcolonial framework to unveil the underlying assumptions embedded in the messages that are conveyed to “teach” and “prepare” immigrants for the Canadian workplace. In particular, the authors focus on non-white immigrants because they form the majority of immigrants to Canada and at the same time data show that they experience particular socio-economic obstacles in their settlement process that European immigrants did not.

Design/methodology/approach

The authors apply postcolonialism as the theoretical framework. This approach allows the authors to analyze the relationship between the local subject and the encounter with the non-local other, in this case the immigrant who is from a non-European background. The authors conduct a Foucauldian critical discourse analysis on selected texts that serve as information sources for immigrants. These texts include government documents, immigrant information brochures, and workplace information books and booklets.

Findings

The analysis shows ideological positions that reveal discursive messages representing the non-white immigrant in binary terms. Such immigrants are represented in opposing (and inferior) terms to the local (largely white) Canadian citizen. By adopting a postcolonial lens, the analysis shows that the messages to acculturate immigrants reveal assimilationist features.

Research limitations/implications

The authors acknowledge that the authors’ own personal socio-political, intellectual, and ideological locations influence the approach, logic, research process, and the interpretation of the findings. For future research, other textual sources should be analyzed with regard to the messages they convey to immigrants as a form of education to see what kind of acculturation is conveyed.

Practical implications

This paper sheds light on the necessity to develop policies that not only aim to acculturate immigrants using integration strategies but also to carefully communicate and educate newcomers through messages that that do not stem from colonial assumptions.

Originality/value

This research points out the taken-for granted and oftentimes invisible forms of discriminatory practices in the workplace that appear non-discriminatory on the surface but are rooted in colonial thinking. Consequently, the authors challenge “mainstream” management theories concerning diversity in the workplace by questioning the underlying messages portrayed to immigrants.
The living wage as an income range for decent work and life
Authors: Yao Christian , Parker Jane , Arrowsmith James , Carr Stuart C.
Published: September 2017

Purpose

A “living” wage (LW) is conventionally defined as enabling meaningful participation in society above subsistence through, for example, recreation, supporting a family, and savings. There is increasing debate over LWs due to growing inequality, rising living costs and welfare reform but this remains largely framed by the econometric cost-benefit parameters that apply to minimum wage regulation. The capabilities approach advocated by Sen (1999) offers a different perspective that is inclusive of choice, contingencies and the inter-connections between quality of (paid) work and private life. The paper aims to discuss these issues.

Design/methodology/approach

The paper adopts this framework and utilises a qualitative exploration of the narratives of 606 New Zealand employees to understand perceived wage effectiveness. The results suggest that a focus on a specific LW rate might be conceptually limiting, in comparison to a LW range.

Findings

First, the findings indicate that there is a pivot range in which people move from self-assessed “survival” to “decent” income. Second, a LW may have more than a simply monetary effect in better meeting employees’ living costs; it can also improve well-being through subjective perceptions of valued freedoms to do with job satisfaction, equity and security.

Originality/value

The results thus draw attention to a wider notion of a LW in terms of personal and family well-being, utilising a capabilities approach, with implications for organisational practice, policy and theory concerning sustainable livelihood and the UN Sustainable Development Goals.
Living wages: a US perspective
Authors: Luce Stephanie
Published: September 2017

Purpose

The purpose of this paper is to provide background on the US living wage movement, with particular attention to recent victories, and also the ways in which the US movement differs from living wage movements in other countries. It begins with some technical distinctions of terms, then analyzes the campaigns and movement for higher wages, and considers some of the challenges the campaigns have faced. It will conclude with some discussion about the future of the movement.

Design/methodology/approach

This is a general review of living wage campaigns in the USA. This is based on a review of existing literature and the author’s own prior research and participant observation.

Findings

The author argues that the initial living wage movement that began in the early 1990s was limited in scope but successful in building coalitions and political power to launch a much more expansive movement to raise wages in 2012.

Originality/value

This paper is a general summary of the last 20 years of living wage campaigns. It does not include new research.
Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study
Authors: Leurquin‐Sterk Gil , Ceccarini Jenny , Crunelle Cleo Lina , Weerasekera Akila , de Laat Bart , Himmelreich Uwe , Bormans Guy , Van Laere Koen
Published: September 2017

Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single‐session [18F]fallypride and [18F]FPEB positron emission tomography, respectively. Additionally, baseline and postalcohol glutamate and glutamine levels in the anterior cingulate cortex (ACC) were measured by using proton‐magnetic resonance spectroscopy. To investigate differences in reward domains linked to both neurotransmitters, regional imaging data were related to subjective alcohol responses. Alcohol induced significant [18F]fallypride displacement in the prefrontal cortex (PFC), temporal and parietal cortices and thalamus (P < 0.05, corrected for multiple comparisons). Dopamine release in the ACC and orbitofrontal and ventromedial PFCs were correlated with subjective ‘liking’ and ‘wanting’ effects (P < 0.05). In contrast, baseline mGluR5 availability was positively correlated with the ‘high’ effect of alcohol in dorsolateral, ventrolateral and ventromedial PFCs and in the medial temporal lobe, thalamus and caudate nucleus (P < 0.05). Although neither proton‐magnetic resonance spectroscopy glutamate nor glutamine levels were affected by alcohol, baseline ACC glutamate levels were negatively associated with the alcohol ‘liking’ effect (P < 0.003). These data reveal new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal dopamine release may encode alcohol ‘liking’ and ‘wanting’ effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal–temporal–subcortical regions is more related to the alcohol ‘high’ effect.
Phosphorylated SNAP25 in the CA1 regulates morphine‐associated contextual memory retrieval via increasing GluN2B‐NMDAR surface localization
Authors: Wang Xinjuan , Liu Yan , Jia Meng , Sun Xiaowei , Wang Na , Li Yijing , Cui Cailian
Published: September 2017

Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B‐containing N‐methyl‐d‐aspartate receptor (GluN2B‐NMDAR) play crucial roles in morphine‐associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2B protein expression in the hippocampal CA1 after morphine conditioned place preference (CPP) expression in rats. Interestingly, we also found that phosphorylation of SNAP25 at Ser187 (pSer187‐SNAP25), a PKC‐activated target, was significantly increased following morphine CPP expression. Blocking the pSer187‐SNAP25 by intra‐CA1 injection of an interfering peptide impaired morphine CPP expression and accompanied by the reduced ratio of GluN2B membrane/total in the CA1. In addition, intra‐CA1 blockade of pSer187‐SNAP25 did not affect natural learning and memory process as evidenced by intact sucrose‐induced CPP expression and normal locomotor activity in rats. Therefore, our results reveal that enhanced pSer187‐SNAP25 by PKC recruits GluN2B‐NMDAR to the membrane surface in the hippocampal CA1 and mediates context‐induced addiction memory retrieval. Our findings in this study fill in the missing link and provide better understanding of the molecular mechanisms involved in morphine‐associated contextual memory retrieval.
Hydroxycarbamide in children with sickle cell anaemia after first‐dose vs. chronic therapy: pharmacokinetics and predictive models for drug exposure
Authors: Estepp Jeremie H. , Wiczling Paweł , Moen Joseph , Kang Guolian , Mack Joana Marie , Liem Robert , Panepinto Julie A. , Garg Uttam , Kearns Gregory , Neville Kathleen A.
Published: September 2017

Aims

The purposes of this work were to: (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew) vs. those receiving chronic therapy (HCchronic), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements.

Methods

Utilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single‐Dose (SD) and Steady‐State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration vs. time profiles were evaluated with a model independent approach in the HCnew and HCchronic groups. Various predictive scenarios were analysed to evaluate whether systemic exposure with hydroxycarbamide could be accurately predicted.

Results

Absorption of hydroxycarbamide was rapid, variable and dose independent. Dose‐normalized peak plasma concentrations and drug exposure (AUC) were higher, and weight‐normalized apparent oral clearance was lower in the HCnew group. We assessed a PK‐guided dosing strategy along with other predictive scenarios and found that inclusion of plasma samples only slightly improved the accuracy of AUC predictions when compared to a population‐based method.

Conclusions

Children naïve to hydroxycarbamide exhibit a different PK profile compared to children receiving chronic therapy. Accuracy of population‐based dosing is sufficient to target AUCs in individual patients. Further clearance/bioavailability studies are needed to address the factors responsible for variability in the disposition of hydroxycarbamide.
Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance
Authors: Powis Z. , Farwell Hagman K.D. , Mroske C. , McWalter K. , Cohen J.S. , Colombo R. , Serretti A. , Fatemi A. , David K.L. , Reynolds J. , Immken L. , Nagakura H. , Cunniff C.M. , Payne K. , Barbaro‐Dieber T. , Gripp K.W. , Baker L. , Stamper T. , Aleck K.A. , Jordan E.S. , Hersh J.H. , Burton J. , Wentzensen I.M. , Guillen Sacoto M.J. , Willaert R. , Cho M.T. , Petrik I. , Huether R. , Tang S.
Published: September 2017

Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.
Lung transplantation in cystic fibrosis patients in Israel: The importance of ethnicity and nutritional status
Authors: Levine Hagit , Prais Dario , Raviv Yael , Rusanov Victorya , Rosengarten Dror , Saute Milton , Hoshen Moshe , Mussaffi Huda , Blau Hannah , Kramer Mordechai R.
Published: September 2017

Objectives

To assess the characteristics that correlate with better outcomes after lung transplantation for patients with cystic fibrosis (CF).

Methods

We retrospectively reviewed the charts of all patients with CF who underwent lung transplantation between 1996 and 2014 at Rabin Medical Center, Israel.

Results

Fifty patients with CF underwent 55 lung transplantations. Eighteen patients (36%) died during the study period. Actuarial survival was 83%, 68%, 62%, and 39% at 1, 3, 5, and 10 years, respectively. Better survival correlated with: BMI at 6 months and 1 year after transplantation (P = .002 and P = .003, respectively), ischemic time of less than 300 minutes (P = .023), absence of liver disease (P = .012), and Jewish compared to Arab ethnicity (P = .007). Freedom from bronchiolitis obliterans syndrome (BOS) was 87%, 75%, and 72% at 1, 3, and 5 years, respectively. BOS was more common and appeared earlier in the Arab than in the Jewish population (P = .012, P = .007). Additionally, prolonged time free of BOS correlated with male gender (P = .039), older age (P < .001), absence of liver disease (P = .012), and higher BMI 1 year after transplantation (P < .001).

Conclusions

Clinically important determinants for survival include BMI pre‐ and 1‐year post‐transplantation and improved freedom from BOS. Arab ethnicity correlated with higher incidence and earlier onset of BOS compared to Jewish ethnicity in Israel.