bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing Strengths and Weaknesses in Dimensional Psychiatry
Authors: Alexander Lindsay M. , Salum Giovanni A. , Swanson James M. , Milham Michael P.
Published: October 2017

Objective

To evaluate the feasibility and value of creating an extensible framework for psychiatric phenotyping that indexes both strengths and weaknesses of behavioral dimensions. The Extended Strengths and Weaknesses Assessment of Normal Behavior (E-SWAN) reconceptualizes each diagnostic criterion for selected DSM-5 disorders as a behavior, which can range from high (strengths) to low (weaknesses). Initial efforts have focused on Panic Disorder, Social Anxiety, Major Depression, and Disruptive Mood Dysregulation Disorder.

Methods

Data were collected from 523 participants (ages: 5-21 years old) in the Child Mind Institute Healthy Brain Network − an ongoing community-referred study. Parents completed each of the four E-SWAN scales and traditional unidirectional scales addressing the same disorders. Distributional properties, Item Response Theory Analysis (IRT) and Receiver Operating Characteristic (ROC) curves (for diagnostic prediction) were used to assess and compare the performance of E-SWAN and traditional scales.

Results

In contrast to the traditional scales, which exhibited truncated distributions, all four E-SWAN scales were found to have near-normal distributions. IRT analyses indicate the E-SWAN subscales provided reliable information about respondents throughout the population distribution; in contrast, traditional scales only provided reliable information about respondents at the high end of the distribution. Predictive value for DSM-5 diagnoses was comparable to prior scales.

Conclusion

E-SWAN bidirectional scales can capture the full spectrum of the population distribution for DSM disorders. The additional information provided can better inform examination of inter-individual variation in population studies, as well as facilitate the identification of factors related to resiliency in clinical samples.
Optical crosstalk in SPAD arrays for high-throughput single-molecule fluorescence spectroscopy
Authors: Ingargiola Antonino , Segal Maya , Gulinatti Angelo , Rech Ivan , Labanca Ivan , Maccagnani Piera , Ghioni Massimo , Weiss Shimon , Michalet Xavier
Published: October 2017

Single-molecule fluorescence spectroscopy (SMFS), based on the detection of individual molecules freely diffusing through the excitation spot of a confocal microscope, has allowed unprecedented insights into biological processes at the molecular level, but suffers from limited throughput. We have recently introduced a multispot version of SMFS, which allows achieving high-throughput SMFS by virtue of parallelization, and relies on custom silicon single-photon avalanche diode (SPAD) detector arrays. Here, we examine the premise of this parallelization approach, which is that data acquired from different spots is uncorrelated. In particular, we measure the optical crosstalk characteristics of the two 48-SPAD arrays used in our recent SMFS studies, and demonstrate that it is negligible (crosstalk probability ≤ 1.1 10−3) and is undetectable in cross-correlation analysis of actual single-molecule fluorescence data.
Agent-based network model predicts strong benefits to youth-centered HIV treatment-as-prevention efforts
Authors: Mittler John E , Murphy James T , Stansfield Sarah , Peebles Kathryn , Gottlieb Geoffrey S , Goodreau Steven , Herbeck Joshua T
Published: October 2017

We used an agent-based network model to examine the effect of targeting different risk groups with unsuppressed HIV viral load for linkage or re-linkage to HIV-related treatment services in a heterosexual population with annual testing. Our model identifies prevention strategies that can reduce incidence to negligible levels (i.e., less than 0.1 infections per 100 person-years) 20 years after a targeted Treatment-as-Prevention (TasP) campaign. The model assumes that most (default 95%) of the population is reachable (i.e., could, in principle, be linked to effective care) and a modest (default 5% per year) probability of a treated person dropping out of care. Under random allocation or CD4-based targeting, the default version of our model predicts that the TasP campaign would need to suppress viral replication in ~80% of infected people to halt the epidemic. Under age-based strategies, by contrast, this percentage drops to 50% to 60% (for strategies targeting those <30 and <25, respectively). Age-based targeting did not need to be highly exclusive to yield significant benefits; e.g. the scenario that targeted those <25 years old saw ~80% of suppressed individuals fall outside the target group. This advantage to youth-based targeting remained in sensitivity analyses in which key age-related risk factors were eliminated one by one. As testing rates increase in response to UNAIDS 90-90-90 goals, we suggest that efforts to link all young people to effective care could be an effective long-term method for ending the HIV epidemic. Linking greater numbers of young people to effective care will be critical for developing countries in which a demographic “youth bulge” is starting to increase the number of young people at risk for HIV infection.
Specific hippocampal representations are linked to generalized cortical representations in memory
Authors: Yu Jai Y. , Liu Daniel F. , Loback Adrianna , Grossrubatscher Irene , Frank Loren M.
Published: October 2017

Memories link information about specific experiences to more general knowledge that is abstracted from and contextualizes those experiences, but how neuronal activity patterns support this link is not known. Here we show that during memory reactivation in a foraging task with multiple spatial paths, specific hippocampal place representations are concurrently and preferentially reactivated with a subset of prefrontal cortical task representations that generalize across different paths. This link between specific and general representations may serve as a neural substrate for abstraction and task guidance in mammals.
Signaling Networks and Dynamics of Allosteric Transitions in Bacterial Chaperonin GroEL: Implications for Iterative Annealing of Misfolded Proteins
Authors: Thirumalai D. , Hyeon Changbong
Published: October 2017

Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. They describe the response a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the Structural Perturbation Method (SPM), based on phonon propagation in solids, that can be used to determine the signal transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Applications to the bacterial chaperonin GroEL-GroES complex shows that the AWD determined from structures also drive the allosteric transitions dynamically. Both from a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the Iterative Annealing Mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function in a self-consistent manner.
High contrast staining for serial block face scanning electron microscopy without uranyl acetate
Authors: Odriozola Adolfo , Llodrá Jaime , Radecke Julika , Ruegsegger Céline , Tschanz Stefan , Saxena Smita , Stephan Rohr , Zuber Benoît
Published: October 2017

1

Serial block face scanning electron microscopy (SBFSEM) is an increasingly popular method for investigating the three-dimensional ultrastructure of large biological samples. Prior to imaging, samples are typically chemically fixed, stained with osmium and uranyl acetate, and subsequently embedded in resin. The purpose of staining is to provide image contrast and reduce specimen charging under the electron beam, which is detrimental to the quality of imaging. Obtaining, using, and disposing of uranyl acetate is getting increasingly cumbersome in many countries due to new regulations on the handling of radioactive substances. Therefore, we developed an alternative staining procedure that does not rely on the use of uranium or any other radioactive substance. This procedure provides excellent contrast and efficiently reduces specimen charging.
Networking and development idiosyncratic deals
Authors: Guerrero Sylvie , Jeanblanc Hélène Challiol
Published: October 2017

Purpose

The purpose of this paper is to explore the antecedents of development idiosyncratic deals (i-deals) from an organizational politics and a situationist perspective. The paper tests a moderated mediation model in which networking skills is indirectly related to development i-deal in a context of high hierarchical plateau.

Design/methodology/approach

The authors test the research model with a sample of 252 engineers, 88 percent male, who work in an economically wealthy region of France and who are thus well positioned to negotiate development i-deals.

Findings

The authors lead analyses with the Preacheret al.’s macros on SPSS. Results support the hypotheses. The authors find that support-seeking behaviors partially mediate the relationship between networking skills and development i-deals, and that this relationship is significant only in a context of high plateauing.

Originality/value

Overall, this study contributes to a deeper understanding of i-deal antecedents by bridging the literatures on i-deals and careers. It also shows that socially skilled employees are able to seek support and in turn, to proactively negotiate development i-deals. This process is a way to cope with perceptions of hierarchical plateau.
Should we talk? Co-rumination and conversation avoidance in job search
Authors: Haggard Dana L. , da Motta Veiga Serge P. , LaPreze Melody W.
Published: October 2017

Purpose

The purpose of this paper is to adopt an approach/avoidance coping framework to examine the relationships of job search co-rumination (i.e. engaging in repeated and excessive conversations with a friend about job search problems) and job search talk avoidance (i.e. persistently seeking to escape conversations about the job search) on job search intensity and job search procrastination.

Design/methodology/approach

The authors surveyed 196 new labor market entrants (i.e. graduating students) at two points in time during their last semester in college.

Findings

The authors found that job search co-rumination is positively related to job search intensity, while job search talk avoidance is positively related to job search procrastination. Interestingly, though, the expected negative relationships between job search co-rumination and job search procrastination and between job search talk avoidance and job search intensity were not significant.

Practical implications

This study has implications for both job seekers and career counselors. For job seekers, understanding how their communication patterns influence their behaviors (and ultimately their success) can help them to see the benefits of a balanced approach to sharing about their job search. Furthermore, career centers could organize either job search mentoring or peer group programs to help job seekers navigate the intricacies of the job search process.

Originality/value

This study contributes to understanding whether and how talking (or not) with others (i.e. friends and relatives) about one’s job search influences one’s job search behaviors, such as intensity and procrastination.
Enhancing the contribution of volunteering to career commitment with friendship among university students
Authors: Cheung Chau-kiu , Liu Elaine Suk-ching
Published: October 2017

Purpose

Encouraging college students to volunteer is a supposed but uncharted way to contribute to their career commitment. Clarifying the ways of the contribution is therefore necessary. From the social capital perspective, volunteering and network density among friends represent social capital to reinforce each other. Thus, the purpose of this paper is to study the enhancement of the contribution by the density.

Design/methodology/approach

The examination employs a two-wave panel survey of 410 university students to estimate the effects of volunteering and friend network density at Wave 1 on career commitment at Wave 2. Essentially, the examination adjusted for biases due to sample attrition and self-selection into volunteering.

Findings

Volunteering at Wave 1 showed a significant contribution to career commitment at Wave 2. Moreover, the contribution significantly increased with friend network density at Wave 1.

Research limitations/implications

Findings from this panel survey of university students in Hong Kong require future research for substantiation. For instance, such research can apply an experimental design to volunteering to guarantee the internal validity of the contribution of volunteering.

Practical implications

Social capital theory is applicable to the promotion of career commitment. Specifically, optimizing the strength of social capital through the combination of volunteering and friendship is promising.

Originality/value

Empirical support for the application of social capital theory to career development is evident. Particularly, the joint contribution of volunteering and friendship is demonstrable.
Understanding and addressing Islamophobia in organizational settings
Authors: Sekerka Leslie E. , Marar Yacobian Marianne
Published: October 2017

Purpose

The purpose of this paper is to call to public leaders to exercise moral courage in choosing to understand and address phobic biases and prejudicial attitudes toward Muslims in the workplace. With reference to developments in the USA, workplace discrimination is framed as an ethical issue, with Islamophobia viewed as a rapidly growing concern.

Design/methodology/approach

This work is a practical application of existing theory and research in positive organizational scholarship to address the concern of workplace discrimination; specifically Islamophobia. Propositions are developed to depict how public leaders can address Islamophobia and other forms of discrimination by role modeling moral courage.

Findings

The findings show that Islamophobia is an ethical challenge for public leaders, one that can begin to be addressed by exercising character strength that promotes tolerance, civility, and respect. This proactive approach will enable public leaders to serve as pillars of openness, inclusion, and thoughtful regard for others, regardless of organizational members’ faith or culture.

Social implications

The social implications are to encourage discourse among global public leaders, prompting awareness and concern for Islamophobia and promoting more informed paths for productive scholarship.

Originality/value

Studies of workplace discrimination typically focus on race and gender, with few considering how Muslims face increasing Islamophobia. This work adds value to the existing literature by explicitly encouraging public leaders to respond, rather than react, to discrimination with moral competency.
Empirical analysis of how risk management by Korea’s exporting companies affects export performance
Authors: Joo Se-Hwan , Pak Myong-Sop
Published: October 2017

Purpose

The purposes of this paper are as follows. First, the paper investigates the causes of risk and methods for managing it based on previous studies of trade risk and trade risk management. Second, the paper analyses the types and forms of trade risk for exporting companies and investigate the relationship between actual trade risks and perceptions of trade risk. Third, the paper establishes a measurement device for trade risk management and export performance based on previous studies. Fourth, the paper derives the concepts based on the accumulated details to establish a research model and verifies a cause and effect relationship. Fifth, the paper analyses what kind of effect the perception of trade risk exerts on trade risk management. And sixth, the paper analyses the effect of the method of trade risk management on the export performance of exporting companies to shed light on the utility of trade risk management.

Design/methodology/approach

The purpose in this research is to analyse the effects of trade risk management on the export performance of exporting companies. The authors have conducted a review of previous studies about trade risk, trade risk management, and the outcomes thereof. Based on that review, the authors have established a research model, derived hypotheses, and used statistical methods to verify those hypotheses.

Findings

First, the authors analysed the methods of settling payments, transaction terms, the transportation environment, and experience in trade claims and found that they influenced the perceived level of trade risk. Second, exporting companies’ prior perception of trade risk determines which methods of trade risk management are suitable. Third, the analysis of the methods of trade risk management and export performance found that financial performance was influenced more than non-financial performance by trade risk management.

Originality/value

The authors determined whether trade risk management effectively counters the losses incurred as a result of the trade risks faced by exporting countries. The authors used an empirical statistical analysis to comprehensively analyse appropriate trade risk management and export performance. Prior to implementing the empirical analysis, the authors conducted research on trade risk and its management and established a research model and research hypotheses based on a theoretical background of trade risk methods appropriate to the circumstances faced by exporting companies.
Effect of non-tariff measures on international tea trades
Authors: Hwang Chae Won , Lim Song Soo
Published: October 2017

Purpose

The purpose of this paper is to analyze the impacts of differences in sanitary and phytosanitary measures as non-tariff measures (NTMs) in the tea trade between importing and exporting countries. With the progress of trade liberalization, there has been a shift of focus to NTMs as alternative or potential trade barriers.

Design/methodology/approach

In order to quantify an NTM on tea trade and implement its empirical application, this study designed an index of differences in maximum residue levels (MRLs) for the pesticide endosulfan and introduced it into a gravity trade model. The estimation challenges in the presence of heteroscedasticity and many zero-trade flows are resolved by taking the Heckman and Poisson pseudo-maximum likelihood estimators.

Findings

This study found that differences in MRLs, arising from the stricter standards in importing countries lead to a significant decrease in tea trade value. This negative impact of differences in MRLs is found to be slightly less than that of tariffs, implying that in this case, the NTM acts as a policy substitute for import tariffs in the global tea trade.

Originality/value

The main contribution of this study is to suggest and quantify the differences in MRLs across countries as a substantial NTM on the global tea trade and provide its empirical application.
Utilising a scholarship program as a workforce strategy for the community-managed mental health sector
Authors: Foreman Emma , McMillan Sara , Wheeler Amanda
Published: October 2017

Purpose

The community-managed mental health sector needs to meet growing workforce demands. Yet, limited research has explored professional development opportunities and effective recruitment and retention strategies to support sector growth. One strategy is the use of a scholarship program to increase skills and training, via a University qualification. The purpose of this paper is to explore the progress of 19 mental health scholarship students and the impact of the scholarship on career intentions.

Design/methodology/approach

A mixed-methods approach comprising scholarship applications, questionnaires and semi-structured interviews was used to explore the students’ university experiences between February 2013 and January 2015. Course convenors of the Mental Health Program were interviewed. Data were collected across three time-points over 24 months, with each collection informing the next research phase. Data analysis involved thematic analysis and descriptive statistics.

Findings

Deeper knowledge, recognition of experience, new career pathways and improved work practice were benefits. Managing time and study, and work-life balance were the greatest challenges. Completing students displayed a range of internal attributes and accessed external supports. At the time of the study, the scholarships maintained student motivation and intention to work in the sector.

Originality/value

This research provides a deeper understanding of the demographics of the sector’s workforce. Insight into the attributes of completing students was obtained. The benefits realized and the challenges faced by the scholarship recipients will inform ongoing workforce development programs for the community-managed mental health sector.
CRISPR/Cas9‐mediated PBP1 and PBP3 mutagenesis induced significant reduction in electrophysiological response to sex pheromones in male Chilo suppressalis
Authors: Dong Xiao‐Tong , Liao Hui , Zhu Guan‐Heng , Khuhro Sajjad Ali , Ye Zhan‐Feng , Yan Qi , Dong Shuang‐Lin
Published: October 2017

Pheromone‐binding proteins (PBPs) are thought to bind and transport sex pheromones onto the olfactory receptors on the dendrite membrane of olfactory neurons, and thus play a vital role in sex pheromone perception. However, the function of PBPs has rarely been demonstrated in vivo. In this study, two PBPs (PBP1 and PBP3) of Chilo suppressalis, one of the most notorious pyralid pests, were in vivo functionally characterized using insects with the PBP gene knocked out by the CRISPR/Cas9 system. First, through direct injection of PBP‐single guide RNA (sgRNA)/Cas9 messenger RNA into newly laid eggs, a high rate of target‐gene editing (checked with polled eggs) was induced at 24 h after injection, 21.3% for PBP1‐sgRNA injected eggs and 19.5% for PBP3‐sgRNA injected eggs. Second, by an in‐crossing strategy, insects with mutant PBP1 or PBP3 (both with a premature stop codon) were screened, and homozygous mutants were obtained in the G3 generation. Third, the mutant insects were measured for electroantennogram (EAG) response to female sex pheromones. As a result, both PBP mutant males displayed significant reduction in EAG response, and this reduction in PBP1 mutants was higher than that in PBP3 mutants, indicating a more important role of PBP1. Finally, the relative importance of two PBPs and the possible off target effect induced by sgRNA‐injection are discussed. Taken together, our study provides a deeper insight into the function of and interaction between different PBP genes in sex pheromone perception of C. suppressalis, as well as a valuable reference in methodology for gene functional study in other genes and other moth species.
A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals
Authors: Lazzeri C. , Cianchi G. , Mauri T. , Pesenti A. , Bonizzoli M. , Batacchi S. , Chiostri M. , Socci F. , Peris A.
Published: October 2017

Background

Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start.

Methods

Sixty‐nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed.

Results

All patients were transported on ECMO (distance, median 77, range 4–456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2, RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC‐ROC: 0.85, 95% CI: 0.76–0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non‐survivors showed a mean value of 20.1 ± 7.4 (P < 0.001).

Conclusions

Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.
How many cases of disease in a pedigree imply familial disease?
Authors: Dudbridge Frank , Brown Suzanne J. , Ward Lynley , Wilson Scott G. , Walsh John P.
Published: October 2017

The ability to perform whole‐exome and, increasingly, whole‐genome sequencing on large numbers of individuals has led to increased efforts to identify rare genetic variants that affect the risk of both common and rare diseases. In such applications, it is important to identify families that are segregating the rare variants of interest. For rare diseases or rare familial forms of common diseases, pedigrees with multiple affected members are clearly harbouring risk variants. For more common diseases, however, it may be unclear whether a family with a few affected members is segregating a familial disease, is the result of multiple sporadic cases, or is a mixture of familial cases and phenocopies. We provide calculations for the probability that a family is harbouring familial disease, presented in general terms that admit working guidelines for selecting families for current sequencing studies. Using examples motivated by our own studies of thyroid cancer and published studies of colorectal cancer, we show that for common diseases, families with exactly two affected first‐degree relatives have only a moderate probability of segregating familial disease, but this probability is higher for families with three or more affected relatives, and those families should therefore be prioritised in sequencing studies.
Phone calls to an Australian pregnancy and lactation counselling service regarding use of galactagogues during lactation – the MotherSafe experience
Authors: Grzeskowiak Luke E. , Hill Majella , Kennedy Debra S.
Published: October 2017

Galactagogues represent substances used to enhance breast milk production. Between 2001 and 2014 we identified 2034 phone calls regarding the use of galactagogues made to MotherSafe. The majority involved discussion of domperidone (n = 1884; 92.6%), with the remainder relating to metoclopramide (n = 153; 7.5%) or other herbal galactagogues (eg fenugreek, milk thistle; n = 262; 12.9%). A 50% decrease in total calls occurred from 2011 to 2014, while the percentage of calls regarding herbal galactagogues increased from 0% in 2001 to 23% in 2014. These findings support the need for more robust research surrounding the use of galactagogues in clinical practice.
Omalizumab rapidly improves angioedema‐related quality of life in adult patients with chronic spontaneous urticaria: X‐ACT study data
Authors: Staubach P. , Metz M. , Chapman‐Rothe N. , Sieder C. , Bräutigam M. , Maurer M. , Weller K.
Published: October 2017

Background

The X‐ACT study aimed to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of H1‐antihistamines.

Methods

In X‐ACT, a phase III, double‐blind, placebo‐controlled study, CSU patients (18‐75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema‐related QoL, skin‐related QoL impairment, and psychological well‐being were assessed.

Results

Ninety‐one patients were randomized and 68 (omalizumab, n = 35; placebo, n = 33) completed the 28‐week treatment period. At baseline, the mean (SD) total Angioedema QoL (AE‐QoL; 56.2 [18.7] and 59.9 [19.2]) and Dermatology Life Quality Index (DLQI; 14.6 [5.7] and 16.6 [7.3]) score were high in the omalizumab and placebo group, respectively. At Week 4 (after the first treatment), the least squares mean difference in the AE‐QoL and DLQI score between groups was −17.6 (P < .001) and −7.2 (P < .001), respectively. Significant QoL improvements in the omalizumab vs placebo groups continued until Week 28, but returned to placebo levels at the follow‐up visit. The mean (SD) baseline 5‐item World Health Organization Well‐being Index was 10.0 (5.5, omalizumab) and 7.7 (5.3, placebo), which increased above the depression threshold (<13) from Week 4 and throughout with omalizumab but not placebo treatment. Compared to placebo, omalizumab was also associated with decreased fear of suffocation due to angioedema.

Conclusions

Our findings support omalizumab treatment in patients with severe H1‐antihistamine‐refractory CSU with angioedema.
Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta‐analysis
Authors: Caissutti Claudia , Familiari Alessandra , Khalil Asma , Flacco Maria E. , Manzoli Lamberto , Scambia Giovanni , Cagnacci Angelo , D'antonio Francesco
Published: October 2017

Introduction

The aim of this study was to explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome.

Material and methods

Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks of gestation in fetuses with, compared to those without, a small thymus on ultrasound. Secondary outcomes: occurrence of chorioamnionitis, intrauterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and preeclampsia.

Results

Twelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes or with preterm labor were at higher risk of preterm birth before 37 weeks (p = 0.01), or before 34 weeks (p < 0.001) for fetuses with a small fetal thymus compared to those without a small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p < 0.001). Fetuses with small thymus were not at higher risk of intrauterine growth restriction (p = 0.3). A small thymus increased the risk of neonatal sepsis (p = 0.007) and morbidity (p = 0.003), but not the risk of preeclampsia (p = 0.9).

Conclusions

A small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intrauterine growth restriction and preeclampsia.
Neonatal Eating Outcome Assessment: tool development and inter‐rater reliability
Authors: Pineda Roberta , Harris Rachel , Foci Felicia , Roussin Jessica , Wallendorf Michael
Published: October 2017

Aim

To define the process of tool development and revision for the Neonatal Eating Outcome (NEO) Assessment and to report preliminary inter‐rater reliability.

Methods

Tool development consisted of a review of the literature and observations of feeding performance among 178 preterm infants born ≤32 weeks gestation. 11 neonatal therapy feeding experts provided structured feedback to establish content validity and define the scoring matrix. The tool was then used to evaluate feeding in 50 preterm infants born ≤32 weeks of gestation and 50 full‐term infants. Multiple revisions occurred at each stage of development. Finally, six neonatal occupational therapists participated in reliability testing by independently scoring five videos of oral feeding of preterm infants using version 4 of the tool.

Results

The intraclass correlation for the ‘prefeeding’ score was 0.71 (0.37–0.96), and the intraclass correlation for the ‘total’ score was 0.83 (0.56–0.98).

Conclusion

The ‘total’ score had good to excellent reliability. Fleiss’ Kappa scores for all 18 scorable items ranged from slight agreement to moderate agreement. Items with the lowest Kappa scores were revised, and additional feedback from therapists engaged in reliability testing was incorporated, resulting in final version 5.
QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors
Authors: Berger Florine A. , Monadian Nico , de Groot Natasja M. S. , Santbergen Bart , van der Sijs Heleen , Becker Matthijs L. , Broers Annoek E. C. , van Gelder Teun , van den Bemt Patricia M. L. A.
Published: October 2017

Aim(s)

Ciprofloxacin and fluconazole combination therapy is frequently used as prophylaxis for, and treatment of, infections in patients with haematological malignancies. However, both drugs are known to prolong the heart rate‐corrected QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP). Therefore, the aim of the current study was to assess the prevalence of QTc prolongation during ciprofloxacin and fluconazole use. The secondary objective was to determine associated risk factors of QTc prolongation in these patients.

Methods

A prospective observational study was performed in patients admitted to the Erasmus University Medical Centre and treated with ciprofloxacin and fluconazole. A 12‐lead electrocardiogram (ECG) was recorded at the estimated time to peak concentration (Tmax) for the last added drug. The main outcome was the proportion of patients with QTc prolongation during treatment. Data on the following potential risk factors were collected: patient characteristics, serum electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver function and concomitant use of other QTc‐prolonging drugs and cytochrome P450 3A4 inhibitors.

Results

A total of 170 patients were included, of whom 149 (87.6%) were treated for haematological malignancies. The prevalence of QTc prolongation was 4.7%. No risk factors were found to be associated with QTc prolongation. The QTc interval increased by 10.7 ms [95% confidence interval (CI) 7.2, 14.1 ms] during ciprofloxacin and fluconazole combination therapy.

Conclusion

The prevalence of QTc prolongation in patients using ciprofloxacin and fluconazole is low compared with the prevalence in the general population, which varies from 5% to 11%. In addition, no risk factors were found. Given the low prevalence, routine ECG monitoring in patients on this therapy should be reconsidered.
Late Holocene stable isotopic (δ13C and δ15N) records of lacustrine organic matter in Guangdong Province, south China, and their palaeoenvironmental implications
Authors: Zhong Wei , Wei Zhiqiang , Shang Shengtan , Chen Yu , Ye Susu , Tang Xiaowen , Zhu Chan , Ouyang Jun , Xue Jibin
Published: October 2017

This study presents the results of TOC/TN (C/N) ratio, δ13C and δ15N analyses of lake sedimentary organic matter (OM) from the Hedong section, western Guangdong Province in south China, with the objective to reveal the history of hydrological and ecological variations in the region influenced by both the Indian summer monsoon (ISM) and East Asian summer monsoon (EASM). Variations in δ13C and δ15N of sedimentary OM may be closely related to past climatic conditions, which results in variations in surface runoff, lake level, allochthonous and autochthonous sources of OM, and lake productivity. Based on the interpretation of these proxies, four periods, i.e. 4370–4100, 3700–2900, 2400–2100 and 1900–900 cal. a BP, are characterized by low lake level, weakened surface runoff and deteriorated status of terrestrial and aquatic ecosystems, whereas the periods 4100–3700, 2900–2400, 2100–1900 and 900–600 cal. a BP are dominated by high lake level, strengthened surface runoff, and flourishing terrestrial and aquatic plants. A remarkable positive correlation between the δ13C values of the section and the ENSO number record obtained from the tropical Pacific implies that the impact of the ISM is greater than that of the EASM in the study area. The abnormal correspondence between the δ13C and solar activity reconstructed from 10Be and 14C records in GRIP ice‐core occurred from 1500–800 and particularly from 4200–4000 cal. a BP, suggesting that these two cool and dry intervals may be caused by stronger volcanic activities that are recorded in the GISP2 and Dome C ice‐cores. This study reveals that changes in solar insolation and solar activity, as well as changes in oceanic–atmospheric circulation (e.g. the ENSO intensity) and intensive volcano eruptions may have exerted influence on late Holocene climate variability in the study area.
Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25
Authors: Hay Debbie L , Garelja Michael L , Poyner David R , Walker Christopher S
Published: October 2017

The calcitonin/CGRP family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two GPCRs, the calcitonin receptor (CTR) or the calcitonin receptor‐like receptor (CLR). Further diversity arises from heterodimerization of these GPCRs with one of three receptor activity‐modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2 receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1–3 complexes, respectively). Apart from the CGRP receptor, there are only peptide antagonists widely available for these receptors, and these have limited selectivity, thus defining the function of each receptor in vivo remains challenging. Further challenges arise from the probable co‐expression of CTR with the CTR/RAMP complexes and species‐dependent splice variants of the CTR (CT(a) and CT(b)). Furthermore, the AMY1(a) receptor is activated equally well by both amylin and CGRP, and the preferred receptor for AM2/IMD has been unclear. However, there are clear therapeutic rationales for developing agents against the various receptors for these peptides. For example, many agents targeting the CGRP system are in clinical trials, and pramlintide, an amylin analogue, is an approved therapy for insulin‐requiring diabetes. This review provides an update on the pharmacology of the calcitonin family of peptides by members of the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology and colleagues.
Differential effects of selective agonists of neuromedin U1 and U2 receptors in obese and diabetic mice
Authors: Nagai Hiroaki , Kaisho Tomoko , Yokoyama Kotaro , Asakawa Tomoko , Fujita Hisashi , Matsumiya Kouta , Noguchi Jiro , Tsuchimori Kazue , Nishizawa Naoki , Kanematsu‐Yamaki Yoko , Dote Katsuko , Inooka Hiroshi , Sakamoto Jun‐ichi , Ohtaki Tetsuya , Asami Taiji , Takekawa Shiro
Published: October 2017

Background and Purpose

Neuromedin U (NmU) may be a novel target for obesity treatment owing to its anorectic and energy expenditure enhancing effects. Although two receptors, NMU1 and NMU2, are both responsible for the NmU‐mediated anti‐obesity effects, the receptor agonist with the most appropriate profiles for treating obesity and diabetes in terms of efficacy and safety is as yet unknown. Thus, we developed and evaluated novel NMU1/2 receptor‐selective agonists.

Experimental Approach

Efficacy and safety were assessed in mice with diet‐induced obesity (DIO) and those with leptin‐deficient diabetes (ob/ob) through repeated peripheral administration of selective agonists to NMU1 (NMU‐6102) and NMU2 (NMU‐2084), along with non‐selective NMU1/2 agonists (NMU‐0002 and NMU‐6014). We also performed immunohistochemistry for c‐Fos protein expression in the brain to probe their mechanisms of action.

Key Results

Although both non‐selective NMU1/2 agonists and the NMU2‐selective agonist had high efficacy compared with the NMU1‐selective agonist, only the NMU2‐selective agonist led to relatively low adverse effects, such as diarrhoea, in DIO mice. However, the non‐selective NMU1/2 agonist and the NMU1‐selective agonist, but not the NMU2‐selective agonist, were effective in diabetic ob/ob mice. Mechanistically, NMU2‐selective agonists preferentially activate pro‐opiomelanocortin neurons in the hypothalamic arcuate nucleus but not in the paraventricular nucleus.

Conclusions and Implications

These results suggest that an NMU2 receptor‐selective agonist may be a well‐balanced drug for the treatment of obesity and that an NMU1 receptor‐selective agonist may also be beneficial for treating obesity and diabetes once its side effects are minimized.
Insulin‐like growth factor‐1 activates PI3K/Akt signalling to protect human retinal pigment epithelial cells from amiodarone‐induced oxidative injury
Authors: Liao Rifang , Yan Fengxia , Zeng Zhuanping , Wang Haitao , Qiu Kaifeng , Xu Jinying , Zheng Wenhua
Published: October 2017

Background and Purpose

Amiodarone is one of the most effective anti‐arrhythmic drugs available, but its clinical applications are limited by toxic side effects including optic toxicity. The purpose of this study was to investigate the toxic effect of amiodarone on D407 cells (a human retinal pigmented epithelial (RPE) cell line) and the mechanisms of the protective effect of insulin‐like growth factor‐1 (IGF‐1).

Experimental Approach

The involvement of the kinases, Akt and ERK, was analysed by Western blot. Intracellular accumulation of ROS was measured using fluorophotometric quantification. A pharmacological approach with inhibitors was used to investigate the pathways involved in the protective action of IGF‐1.

Key Results

Amiodarone concentration‐dependently augmented the production of ROS, lipid peroxidation and apoptosis in D407 cells. IGF‐1 time‐ and concentration‐dependently reversed these effects of amiodarone and protected D407 cells from amiodarone‐mediated toxicity. Amiodarone inhibited the pAkt but not pErk, and IGF‐1 reversed this inhibitory effect of amiodarone. However, IGF‐1 failed to suppress amiodarone‐induced cytotoxicity in the presence of PI3K/Akt inhibitor LY294002 suggesting the direct involvement of the PI3K/Akt pathway. Furthermore, in vivo rat flash electroretinogram (FERG) recordings showed that IGF‐1 reverses the amiodarone‐induced decrease in a‐ and b‐waves. The immunocytochemistry findings confirmed that vitreous IGF‐1 injections promote the survival of RPE cells in rat retina treated with amiodarone.

Conclusion and Implications

IGF‐1 can protect RPE cells from amiodarone‐mediated injury via the PI3K/Akt pathway in vivo and in vitro. IGF‐1 has potential as a protective drug for the prevention and treatment of amiodarone‐induced optic toxicity.
Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor
Authors: Luo Jiao , Xu Qi , Jiang Bo , Zhang Renshuai , Jia Xiaoling , Li Xiangqian , Wang Lijun , Guo Chuanlong , Wu Ning , Shi Dayong
Published: October 2017

Background and Purpose

Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling by tyrosine dephosphorylation of the insulin receptor. It is a highly validated target for type 2 diabetes therapeutics. Here, the anti‐diabetic effects of HPN were evaluated in the diabetic BKS db mice.

Experimental Approach

The mode of inhibition of PTP1B by HPN was determined according to the Lineweaver–Burk plot. A surface plasmon resonance assay and molecular docking were used to study the interaction between HPN and PTP1B. C2C12 skeletal muscle cells were used to investigate the cell permeability of HPN and the effect of HPN on insulin signalling pathways. Long‐term effects of HPN on glycaemic control were investigated in diabetic BKS db mice. Glycogen contents in liver and muscle were determined. Furthermore, changes in the number of beta cells were evaluated by Gomori staining.

Key Results

HPN was identified as a specific PTP1B inhibitor. HPN directly interacted with PTP1B by binding to the catalytic domain through hydrogen bonds in a competitive mode. Approximately 56.98% of HPN entered into the cultured C2C12 myotubes. HPN ameliorated the impaired insulin signalling in palmitate‐treated C2C12 myocytes. Notably, oral administration of HPN significantly protected mice from hyperglycaemia, dyslipidemia and hyperinsulinaemia. HPN also enhanced the storage of glycogen in liver and muscle. Moreover, HPN obviously improved the beta cell numbers of the pancreatic islets.

Conclusion and Implications

Our results indicate that HPN is a specific PTP1B inhibitor, with anti‐diabetic properties and good cell permeability and oral availability.
Increased T‐helper 17 cell differentiation mediated by exosome‐mediated microRNA‐451 redistribution in gastric cancer infiltrated T cells
Authors: Liu Feng , Bu Zhouyan , Zhao Feng , Xiao Daping
Published: October 2017

MicroRNA (miR)‐451 is a cell metabolism‐related miRNA that can mediate cell energy‐consuming models by several targets. As miR‐451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T‐helper 17 (Th17) cells, we sought to investigate whether miR‐451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real‐time PCR was used for detecting expression of miR‐451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome‐enveloped miR‐451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR‐451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR‐451 was negatively related to infiltrated T cells and exosome miR‐451. Exosome miR‐451 can not only serve as an indicator for poor prognosis of post‐operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR‐451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5′ AMP‐activated protein kinase (AMPK) and increased mTOR activity was investigated in miR‐451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR‐451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR‐451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity.