bluuebunny/crossref_metadata_2025 huggingface dataset:
Findings and Outcomes in a Prevaccination Cohort of Women Younger Than 25 Years Attending a Tertiary Colposcopy Service
Authors: Jayasinghe Yasmin L. , Bhat Rani , Quinn Michael , Wrede C. David H. , Tan Jeffrey H.J.
Published: May 2016

Objective

To describe clinical presentation and treatment in women younger than 25 years referred to the Royal Women’s Hospital colposcopy clinic, before implementation of the National Human Papillomavirus Vaccination Program.

Methods

Retrospective cohort analysis of women younger than 25 years referred to a tertiary hospital colposcopy clinic between 1998 and 2007. Clinical presentation and correlation between cervical cytology, biopsy, and histology at treatment was examined.

Results

Approximately 14,635 colposcopies were undertaken in 4104 women (median age, 22 years); 3051 had abnormal referral cytology, of whom, 23.8% had high-grade disease on punch biopsy. High-grade disease was found in 15.1% of those with possible low-grade or low-grade cytology (293/1932), 42.4% of those with possible high-grade or high-grade cytology (474/1119). Sensitivity and specificity of colposcopy for high-grade disease (high-grade epithelial abnormality, adenocarcinoma in situ, cervical cancer up to 2 years follow-up) was 60.0% and 82.3%, respectively. Thirty-nine percent (n = 1180) with abnormal cytology had treatment, of which, 66.6% was ablative. Histological CIN3+ was found in 53.8% of those with a previous high-grade punch biopsy (126/234) at excisional treatment, and 23.0% of those with a previous low-grade punch biopsy (20/87) (relative risk, 2.3 [CI, 1.6–3.5]). Four cancers were detected (0.1% of the total cohort, 0.5% of those with a high-grade biopsy, and 1.7% of those with a high-grade biopsy who underwent excisional treatment.)

Conclusions

Before vaccination, young women experienced a high real-time burden of high-grade disease and high rates of intervention. These baseline data contribute to monitoring of HPV vaccination and revised cervical screening strategies.
Ramp Study Hemodynamics, Functional Capacity, and Outcome in Heart Failure Patients with Continuous-Flow Left Ventricular Assist Devices
Authors: Jung Mette H. , Gustafsson Finn , Houston Brian , Russell Stuart D.
Published: May 2016

Ramp studies—measuring changes in cardiac parameters as a function of serial pump speed changes (revolutions per minute [rpm])—are increasingly used to evaluate function and malfunction of continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that ramp studies can predict functional capacity, quality of life (QOL), and survival in CF-LVAD patients. Hemodynamic changes per Δrpm were measured at a minimum of CF-LVAD support, at baseline pump speed, and at maximal tolerable pump speed. Subsequently functional capacity and QOL were assessed. Eighty ramp tests were performed in 44 patients (HeartMate II, Thoratec Corporation, Pleasanton, CA). Functional status was evaluated in 70% (31/44); average 6 minute walk test (6MWT) was 312 ± 220 min, New York Heart Association (NYHA) I–II/III–IV (70/30%) and activity scores very low–low/moderate–very high (55/45%). Decrease in pulmonary capillary wedge pressure per Δrpm was related to better NYHA classification; NYHA I–II vs. III–IV, −0.29 ± 0.15 vs. −0.09 ± 0.16 mm Hg/rpm * 10−2 (p = 0.007) as well as to activity score; very low–low vs. moderate–very high, −0.16 ± 0.16 vs. −0.31 ± 0.16 mm Hg/rpm * 10−2 (p = 0.02). Cardiac output change per Δrpm was correlated to measures of QOL. Ramp tests did not predict survival. In conclusion, hemodynamic changes during ramp studies are associated with measures of functional capacity and QOL. Hence, such tests could potentially identify patients in risk of failure to thrive during CF-LVAD support.
Design Rationale and Preclinical Evaluation of the HeartMate 3 Left Ventricular Assist System for Hemocompatibility
Authors: Bourque Kevin , Cotter Christopher , Dague Charles , Harjes Daniel , Dur Onur , Duhamel Julien , Spink Kaitlyn , Walsh Kelly , Burke Edward
Published: May 2016

The HeartMate 3 (HM3) left ventricular assist device (LVAD) is designed to support advanced heart failure patients. This centrifugal flow pump has a magnetically levitated rotor, artificial pulse, textured blood-contacting surfaces, optimized fluid dynamics, large blood-flow gaps, and low shear stress. Preclinical tests were conducted to assess hemocompatibility. A computational fluid dynamics (CFD) model guided design for low shear stress and sufficient washing. Hemolysis testing was conducted on six pumps. Plasma-free hemoglobin (PfHb) and modified index of hemolysis (MIH) were compared with HeartMate II (HMII). CFD showed secondary flow path residence times between 27 and 798 min, comparable with main flow residence times between 118 and 587 min; HM3 vs. HMII shear stress exposure above 150 Pa was 3.3 vs. 11 mm3 within the pump volume and 134 vs. 604 mm2 on surfaces. In in vitro hemolysis tests at 2, 5, and 10 L/min, average pfHb 6 hours after test initiation was 58, 74, and 157 mg/dl, compared with 112, 123, and 353 mg/dl for HMII. The HM3/HMII ratio of average MIH at 2, 5, and 10 L/min was 0.29, 0.36, and 0.22. Eight 60 day bovine implants were tested with average flow rates from 5.6 to 6.4 L/min with no device failures, thrombosis, or hemolysis. Results support advancing HM3 to clinical trials.
Experimental Venoarterial Extracorporeal Membrane Oxygenation Induces Left Ventricular Dysfunction
Authors: Schiller Petter , Vikholm Per , Hellgren Laila
Published: May 2016

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has experienced an increased use in acute cardiac failure. There are some reports on negative effects of VA-ECMO on cardiac function, such as left ventricular (LV) dilatation and cardiac stun, but the support in the literature is scarce. This study investigates the effects of experimental VA-ECMO on LV function in both peripheral and central cannulation. Ten pigs were randomized to VA-ECMO by either peripheral cannulation through the femoral vessels or central cannulation in the right atrium and ascending aorta. Left ventricular performance was measured with pressure-volume catheters during 5 hours of VA-ECMO. The LV end-diastolic and end-systolic volumes increased comparably in both groups during ECMO. Left ventricular ejection fraction, stroke work, and maximum rate of pressure change decreased comparably in both groups as a function of time on ECMO. The site of cannulation had no impact on the LV response to ECMO. In conclusion, VA-ECMO increased LV volumes and reduced LV function, irrespective of cannulation site in this experimental model. Reduced LV ejection fraction and stroke work indicated LV dysfunction during ECMO.
Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in human and nonhuman primates
Authors: Opitz Alexander , Falchier Arnaud , Yan Chao-Gan , Yeagle Erin , Linn Gary , Megevand Pierre , Thielscher Axel , Milham Michael P. , Mehta Ashesh , Schroeder Charles
Published: May 2016

Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information for the interpretation of human TES studies and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.
Genomic Prediction of Hybrid Combinations in the Early Stages of a Maize Hybrid Breeding Pipeline
Authors: Kadam D.C. , Potts S.M. , Bohn M.O. , Lipka A.E. , Lorenz A.J.
Published: May 2016

Prediction of single-cross hybrid performance has been a major goal of plant breeders since the beginning of hybrid breeding. Genomic prediction has shown to be a promising approach, but only limited studies have examined the accuracy of predicting single cross performance. Most of the studies rather focused on predicting top cross performance using single tester to determine the inbred parent’s worth in hybrid combinations. Moreover, no studies have examined the potential of predicting single crosses made among random progenies derived from a series of biparental families, which resembles the structure of germplasm comprising the initial stages of a hybrid maize breeding pipeline. The main objective of this study was to evaluate the potential of genomic prediction for identifying superior single crosses early in the breeding pipeline and optimize its application. To accomplish these objectives, we designed and analyzed a novel population of single-cross hybrids representing the Iowa Stiff Stalk Synthetic/Non-Stiff Stalk heterotic pattern commonly used in the development of North American commercial maize hybrids. The single cross prediction accuracies estimated using cross-validation ranged from 0.40 to 0.74 for grain yield, 0.68 to 0.91 for plant height and 0.54 to 0.94 for staygreen depending on the number of tested parents of the single crosses. The genomic estimated general and specific combining abilities showed a clear advantage over the use of genomic covariances among single crosses, especially when one or both parents of the single cross were untested in hybrid combinations. Overall, our results suggest that genomic prediction of the performance of single crosses made using random progenies from the early stages of the breeding pipeline holds great potential to re-design hybrid breeding and increase its efficiency.
A variant by any name: quantifying annotation discordance across tools and clinical databases
Authors: Yen Jennifer , Garcia Sarah , Montana Aldrin , Harris Jason , Chervitz Steven , West John , Chen Richard , Church Deanna M.
Published: May 2016

Background

Clinical genomic testing is dependent on the robust identification and reporting of variant-level information in relation to disease. With the shift to high-throughput sequencing, a major challenge for clinical diagnostics is the cross-identification of variants called on their genomic position to resources that rely on transcript- or protein-based descriptions.

Methods

We evaluated the accuracy of three tools (SnpEff, Variant Effect Predictor and Variation Reporter) that generate transcript and protein-based variant nomenclature from genomic coordinates according to guidelines by the Human Genome Variation Society (HGVS). Our evaluation was based on comparisons to a manually curated list of 127 test variants of various types drawn from data sources, each with HGVS-compliant transcript and protein descriptors. We further evaluated the concordance between annotations generated by Snpeff and Variant Effect Predictor with those in major germline and cancer databases: ClinVar and COSMIC, respectively.

Results

We find that there is substantial discordance between the annotation tools and databases in the description of insertion and/or deletions. Accuracy based on our ground truth set was between 80-90% for coding and 50-70% for protein variants, numbers that are not adequate for clinical reporting. Exact concordance for SNV syntax was over 99.5% between ClinVar and Variant Effect Predictor (VEP) and SnpEff, but less than 90% for non-SNV variants. For COSMIC, exact concordance for coding and protein SNVs were between 65 and 88%, and less than 15% for insertions. Across the tools and datasets, there was a wide range of equivalent expressions describing protein variants.

Conclusion

Our results reveal significant inconsistency in variant representation across tools and databases. These results highlight the urgent need for the adoption and adherence to uniform standards in variant annotation, with consistent reporting on the genomic reference, to enable accurate and efficient data-driven clinical care.
Retrieving chromatin patterns from deep sequencing data using correlation functions
Authors: Molitor Jana , Mallm Jan-Philipp , Rippe Karsten , Erdel Fabian
Published: May 2016

Epigenetic modifications and other chromatin features partition the genome on multiple length scales. They define chromatin domains with distinct biological functions that come in sizes ranging from single modified DNA bases to several megabases in case of heterochromatic histone modifications. Due to chromatin folding, domains that are well separated along the linear nucleosome chain can form long-range interactions in three-dimensional space. It has now become a routine task to map epigenetic marks and chromatin structure by deep sequencing methods. However, assessing and comparing the properties of chromatin domains and their positional relationships across data sets withouta prioriassumptions remains challenging. Here, we introduce multi-scale correlation evaluation (MCORE), which uses the fluctuation spectrum of mapped sequencing reads to quantify and compare chromatin patterns over a broad range of length scales in a model-independent manner. We applied MCORE to map the chromatin landscape in mouse embryonic stem cells and differentiated neural cells. We integrated sequencing data from chromatin immunoprecipitation, RNA expression, DNA methylation and chromosome conformation capture experiments into network models that reflect the positional relationships among these features on different genomic scales. Furthermore, we used MCORE to compare our experimental data to models for heterochromatin reorganization during differentiation. The application of correlation functions to deep sequencing data complements current evaluation schemes and will support the development of quantitative descriptions of chromatin networks.
Evidence for reassortment of highly divergent novel rotaviruses from bats in Cameroon, without evidence for human interspecies transmissions
Authors: Yinda Claude Kwe , Zeller Mark , Conceição-Neto Nádia , Maes Piet , Deboutte Ward , Beller Leen , Heylen Elisabeth , Ghogomu Stephen Mbigha , Ranst Marc Van , Matthijnssens Jelle
Published: May 2016

Bats are an important reservoir for pathogenic human respiratory and hemorrhagic viruses but only little is known about bat viruses causing gastroenteritis in humans, including rotavirus A strains (RVA). Only three RVA strains have been reported in bats in Kenya (straw-colored fruit bat) and in China (lesser horseshoe and a stoliczka’s trident bat), being highly divergent from each other. To further elucidate the potential of bat RVAs to cause gastroenteritis in humans we started by investigating the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using metagenomics. Five samples contained significant numbers of RVA Illumina reads, sufficient to obtain their (near) complete genomes. A single RVA strain showed a close phylogenetic relationship with the Kenyan bat RVA strain in six gene segments, including VP7 (G25), whereas the other gene segments represented novel genotypes as ratified by the RCWG. The 4 other RVA strains were highly divergent from known strains (but very similar among each other) possessing all novel genotypes. Only the VP7 and VP4 genes showed a significant variability representing multiple novel G and P genotypes, indicating the frequent occurrence of reassortment events.

Comparing these bat RVA strains with currently used human RVA screening primers indicated that several of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel VP6 based screening primers matching both human and bat RVAs were developed and used to screen samples from 25 infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, Sanger sequencing did not indicate evidence of interspecies transmissions.

This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.
Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task
Authors: MacQueen David A. , Dalrymple Savannah R. , Drobes David J. , Diamond David M.
Published: May 2016

Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-d-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load-dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two-comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory.
Determinants of compliance with AAOIFI standards by Islamic banks
Authors: El-Halaby Sherif , Hussainey Khaled
Published: May 2016

Purpose

The authors explore the level and determinants of compliance with Accounting and Auditing Organization for Islamic Financial Institution’s (AAOIFI) financial and governance standards by Islamic banks (IBs).

Design/methodology/approach

The sample consists of 43 IBs across eight countries. The authors use ordinary least squares regression analyses to examine the impact of bank-specific characteristics and corporate governance (CG) mechanisms concerned with Board of Directors (BOD) and Sharia Supervisory Board (SSB) on the levels of compliance with AAOIFI standards.

Findings

The paper finds that the average compliance level based on AAOIFI standards concerning the SSB is 68 per cent; corporate social responsibility (CSR) is 27 per cent; and presentation of financial statements (FSs) is 73 per cent. The aggregate disclosure based on the three indices is 56 per cent. The analysis also shows that size, existing Sharia-auditing department, age and CG of SSB are the main determinants of compliance levels.

Originality/value

The determinants of compliance with AAOIFI standards for IBs around the world have not been explored before, and therefore, this paper is the first of its kind to this issue.
Dispute resolution in the Islamic banking industry of Tanzania: learning from other jurisdictions
Authors: Hikmany Abdul-Nasser H.R. , Oseni Umar A.
Published: May 2016

Purpose

This paper aims to examine the prospects of a dispute resolution framework for the Islamic banking industry in Tanzania under the existing legal framework.

Design/methodology/approach

This paper is based on comparative study by drawing significant lessons from other jurisdictions, and argues that to avoid some of the initial drawbacks in the dispute resolution framework for Islamic banking transactions in more advanced jurisdictions like Malaysia and United Kingdom, it is important for Tanzania to get it right from the onset to effectively manage Islamic banking disputes.

Findings

The study finds that apart from the court system which provides the main avenue for Islamic finance litigation, other processes such as arbitration and mediation which are deemed to be more sustainable could also be developed for effective dispute management.

Research limitations/implications

The study focuses on Tanzania banking system with comparison to other jurisdictions.

Practical implications

An increase of Sharī’ah-compliant products in Tanzania has led to the establishment of a number of Islamic banks. This study demonstrates the need for Tanzania to make use and/or make adjustment of its laws for effective dispute settlement of banking-related disputes.

Originality/value

This study appears to be the first paper to draw significant experiences from other jurisdictions to resolve Islamic banking disputes in Tanzania. It is expected to provide a good policy framework for the stakeholders in the Islamic banking industry in Tanzania.
Retrospective: a cross-sectional test of the effect and conceptualization of service value revisited
Authors: Cronin J. Joseph
Published: May 2016

Purpose

This paper aims to provide an evaluation of the findings first put forward in the article “A cross-sectional test of the effect and conceptualization of service value” with the benefit of hindsight, and to offer directions for further research and developments in the research area.

Design/methodology/approach

Research directions which emanated from the publication of the paper have been examined in the light of current service(s) marketing theory and practice. As a result, promising current and future strands of research have been identified.

Findings

The focus of both the original and this paper is on the conceptualization and measurement of the value construct. Although much theory has been advanced relative to the measurement of value, the marketing literature lacks a conceptualization and measures that reflect this theory.

Research limitations/implications

The implication of the paper is that marketing scholars tend to focus more on to other studies before exhausting the opportunities to identify and test appropriate conceptualizations and measures of core marketing constructs such as value, quality, sacrifice and satisfaction.

Practical implications

Although value is universally identified as a major driver of consumer decision-making, a full appreciation of its role in the strategic marketing efforts of organizations depends on having an accurate conceptualization and measures. The original paper and this revisit motivate and assist organizations in their efforts to better understand value and its impact in the decisions made by consumers.

Social implications

To contribute to the needs and wants of society, organizations must identify what is valued by society. The original and this revisit identify the creation of value as a basic need in encouraging consumer behaviours when the intent is to satisfy societal needs or desires.

Originality/value

The original paper was highly rated, and generated discussion and important further research. It has value as part of the history of service marketing research. The retrospective analysis by the authors gives a unique insight into processes and thinking associated with understanding key aspects that contribute to the historical development of service marketing, and provides substantial food for thought for future research directions.
A Changing UK in a Changing Europe: The UK State between European Union and Devolution
Authors: Minto Rachel , Hunt Jo , Keating Michael , Mcgowan Lee
Published: May 2016

Two issues currently dominate the UK's constitutional landscape: the UK's membership of the European Union (EU) on the one hand; and the unsettled constitutional settlements between the UK and the devolved administrations of Scotland, Wales and Northern Ireland on the other. This article considers these two issues in concert. It stresses the distinct relationships between the EU and the devolved territories within the UK—concerning both devolved and non‐devolved policy areas—highlighting the salience of a devolved perspective in any consideration of UK–EU relations. Despite its importance, sensitivity to this has been lacking. The article explores the implications of a ‘Leave’ or ‘Remain’ outcome on the future of the internal territorial dynamics within the UK. While there are too many unknowns to be certain of anything, that there will be knock‐on effects is, however, beyond doubt.
Effects of Prohibition and Decriminalization on Drug Market Conflict
Authors: Jacques Scott , Rosenfeld Richard , Wright Richard , van Gemert Frank
Published: May 2016

Research Summary

To reduce individual and social harms, most nations prohibit certain psychoactive drugs. Yet, prior scholarship has suggested that prohibition reduces illicit drug sellers’ access to law and thereby increases predation against and retaliation by them. No prior study, however, has directly tested that theory by comparing drug sellers of different legal statuses operating in a single place and time. This study analyzes rates of victimization, legal mobilization, and violent retaliation in three retail drug markets in Amsterdam, the Netherlands: the legally regulated alcohol trade of cafés, the decriminalized cannabis market of “coffeeshops,” and the illegal street drug market. Results from interviews conducted with 50 sellers in each market indicate, as expected, that illicit drug dealers have the highest rates of victimization and violent retaliation and the lowest rates of legal mobilization. Contrary to expectations, we find coffeeshops experience less victimization than cafés and have similar rates of violent retaliation and legal mobilization.

Policy Implications

Our findings suggest that state regulation of drug markets affects victimization and conflict management of sellers, but the relationship does not seem to be linear. Prohibition undercuts the state's regulatory capacity by producing zones of virtual statelessness in which formal means of dispute resolution are unavailable, and thus, victimization and retaliation are more common. At the other extreme is laissez faire regulation, which may make sellers more likely to address problems only after they occur (instead of preventing their occurrence). The Dutch government originally instituted coffeeshops as a harm‐reduction method meant to separate the market for cannabis from that of hard drugs. The policy also seems to work well when it comes to reducing victimization, perhaps by encouraging the use of preventive measures by coffeeshop owners and employees. The Dutch experience offers lessons for drug policy reforms elsewhere.
Sacral nerve stimulation for faecal incontinence: medium‐term follow‐up from a single institution
Authors: Patton Vicki , Abraham Earl , Lubowski David Z.
Published: May 2016

Background

Most studies on sacral nerve stimulation (SNS) are either single‐centre with small numbers of patients or multi‐centre studies. We present the medium‐term follow‐up results from a single centre for 127 patients undergoing SNS.

Methods

Consecutive patients treated with SNS for faecal incontinence had preoperative baseline St Mark's continence scores, faecal incontinence quality of life (FIQL) measures and anorectal physiology studies. Follow‐up was a postal questionnaire concerning continence, FIQL, patient‐perceived change in bowel control (−5 to +5 where 0 is no change), overall satisfaction (0–10 visual analogue scale) and use of medications.

Results

A total of 166 patients underwent temporary nerve stimulation testing, of which 112 progressed to a permanent implantable pulse generator (IPG). Fifteen received an IPG without the testing phase, hence 127 patients in total. Fourteen had the IPG removed, four were deceased, leaving 109 for assessment; 91 (83%) responded to the survey. Mean follow‐up was 2.7 years (range: 2 months–8.5 years). Mean baseline St Mark's continence score was 14.4, and mean follow‐up score was 10.3 (P < 0.01). FIQL improved in all domains (P < 0.001). Patient‐reported improved bowel control mean score was +3.2 (95% CI: 2.9, 3.55). Median satisfaction score was 8.0 (range: 0–10). Complications included 17 lead dislodgements, seven superficial infections, five infections requiring surgery and five repositioning of a rotated IPG. Thirty‐two patients used loperamide and 34 used fibre supplements.

Conclusion

In this observational study, limited by the absence of a placebo control group, SNS significantly improved continence and quality of life, and patient satisfaction was high.
Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis
Authors: Dellon E. S. , Higgins L. L. , Beitia R. , Rusin S. , Woosley J. T. , Veerappan R. , Selitsky S. R. , Parker J. S. , Genta R. M. , Lash R. H. , Aranda R. , Peach R. J. , Grimm M.
Published: May 2016

Background

Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non‐invasive biomarker.

Aim

To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL‐13 levels.

Methods

This was a sub‐analysis of a prospective cohort study of adults undergoing out‐patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post‐treatment levels were compared for cases. Serum IL‐13 and tissue expression of periostin were also assessed.

Results

A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post‐treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL‐13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07).

Conclusions

Serum periostin levels were similar in cases and controls, and there were no changes post‐treatment. Given elevated IL‐13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti‐IL‐13 therapy.
Making Sense of Class: A Commentary on Lott
Authors: Keefer Lucas A. , Goode Chris
Published: May 2016

While Lott's commentary rightly calls for greater attention to the consequences of capitalism, we offer further discussion of one important issue: the psychological study of social class. This work has predominantly focused on the psychological consequences of class itself by studying the ways that objective and subjective status differences influence thought and behavior. We call for a broader approach that further acknowledges the psychology of class perceptions and beliefs, one means of legitimizing (or challenging) inequality under capitalism. The role of class beliefs as a justification of, or challenge to, the status quo presents an important area for future research. (100/100)
Curcumin Inhibits 5‐Fluorouracil‐induced Up‐regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development
Authors: Sakai Hiroyasu , Kai Yuki , Oguchi Aya , Kimura Minami , Tabata Shoko , Yaegashi Miyabi , Saito Taiki , Sato Ken , Sato Fumiaki , Yumoto Tetsuro , Narita Minoru
Published: May 2016

The compound 5‐fluorouracil (5‐FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C‐X‐C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5‐FU in mice. Curcumin has anti‐inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5‐FU‐induced diarrhoea development and CXCL1 and CXCL2 up‐regulation in the colon. Mice were given 5‐FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5‐FU and administered 30 min. before the administration of 5‐FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real‐time RT‐PCR. Curcumin reduced the 5‐FU‐induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up‐regulated by 5‐FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5‐FU application in vitro. The 5‐FU‐induced up‐regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay‐117082 and bortezomib, nuclear factor kappa B (NF‐κB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element‐binding protein–histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF‐κB and HAT activation.
Regulatory Focus, Task Engagement and Divergent Thinking
Authors: Beuk Frederik , Basadur Tim
Published: May 2016

We investigate the effect of individuals’ regulatory focus on divergent thinking performance. We analysed 3576 ideas, generated by 341 English‐speaking adults who participated in two separate divergent thinking tasks. A promotion focus results in higher levels of creative potential. Based on regulatory fit theory, we find that task engagement mediates the positive effect of a promotion focus on creative potential. Our findings are robust regardless whether fluency, flexibility or uniqueness is used as the creative potential measure. Our study further uncovers that regulatory focus does not only change the quantity of ideas, but also impacts the type of ideas generated. Promotion focus individuals generate a broader range of ideas than prevention focus individuals.
Induction of apoptosis by HBI‐8000 in adult T‐cell leukemia/lymphoma is associated with activation of Bim and NLRP3
Authors: Hasegawa Hiroo , Bissonnette Reid P. , Gillings Mireille , Sasaki Daisuke , Taniguchi Hiroaki , Kitanosono Hideaki , Tsuruda Kazuto , Kosai Kousuke , Uno Naoki , Morinaga Yoshitomo , Imaizumi Yoshitaka , Miyazaki Yasushi , Yanagihara Katsunori
Published: May 2016

Adult T‐cell leukemia/lymphoma (ATL) is an aggressive T‐cell malignancy caused by human T‐cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti‐chemokine (C‐C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI‐8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T‐cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI‐8000 on ATL‐derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI‐8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in HBI‐8000‐induced ATL cell death. Further investigations using siRNAs confirmed that Bim contributes to HBI‐8000‐induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI‐8000 in patients with ATL. Although the role of NLRP3 inflammasome activation in ATL cell death remains to be verified, HBI‐8000 may be part of a novel therapeutic strategy for cancer based on the NLRP3 pathway.
Is small‐scale agriculture really the main driver of deforestation in the Peruvian Amazon? Moving beyond the prevailing narrative
Authors: Ravikumar Ashwin , Sears Robin R. , Cronkleton Peter , Menton Mary , Pérez‐Ojeda del Arco Matías
Published: May 2016

A key premise underlying discussion about deforestation in Amazonian Peru is that small‐scale or so‐called migratory agriculture is the main driver of deforestation. This premise has been expressed in government documents and public outreach events. How the Peruvian government understands drivers of deforestation in the Amazon has profound implications for how it will confront the problem. It is therefore important to critically revisit assumptions underlying this narrative. We find that the narrative is based on remote sensing of deforestation patch sizes but not on field data, potentially conflating distinct drivers of deforestation under the umbrella of “migratory,” “small‐scale,” or “subsistence” agriculture. In fact, small patches of deforested land may indicate any number of processes, including sustainable fallow management and agroforestry. Moreover, the data underlying the narrative tell us little about the actors driving these processes or their motivations. Different processes have distinct implications for environmental sustainability and require targeted policy responses. We unpack these diverse actors, geographies, and motivations of small‐patch deforestation in the Peruvian Amazon and argue that differentiating among these drivers is necessary to develop appropriate policy responses. We call for researchers to revisit assumptions and critically assess the motivations of observed deforestation to appropriately target policy action.
Outpatient diabetes clinical decision support: current status and future directions
Authors: O'Connor P. J. , Sperl‐Hillen J. M. , Fazio C. J. , Averbeck B. M. , Rank B. H. , Margolis K. L.
Published: May 2016

Outpatient clinical decision support systems have had an inconsistent impact on key aspects of diabetes care. A principal barrier to success has been low use rates in many settings. Here, we identify key aspects of clinical decision support system design, content and implementation that are related to sustained high use rates and positive impacts on glucose, blood pressure and lipid management. Current diabetes clinical decision support systems may be improved by prioritizing care recommendations, improving communication of treatment‐relevant information to patients, using such systems for care coordination and case management and integrating patient‐reported information and data from remote devices into clinical decision algorithms and interfaces.
How Incomplete Contracts Foster Innovation in Inter‐Organizational Relationships
Authors: Sumo Regien , van der Valk Wendy , van Weele Arjan , Duysters Geert
Published: May 2016

Relative to relational governance, research into the use and effects of formal governance is scarce. Recent contributions suggest that a specific type of contract that has intentionally been left incomplete, the performance‐based contract (PBC), fosters innovation. However, it is unknown how this effect occurs. To address this gap, we draw on transaction cost economics and agency theory to develop propositions on how PBCs affect innovation. PBCs are characterized by low term specificity and rewards that are tied to performance. We propose that low term specificity, that is, not stipulating how the focal firm's partner should deliver the performance and which resources to use, enhances the partner's autonomy, which in turn fosters innovation. However, excessive low term specificity inhibits innovation, since it may lead the partner to display opportunistic behavior. We furthermore propose that performance‐based pay incentivizes the partner to engage in innovation. This suggests that linking rewards to performance attenuates the negative relationship between term specificity and innovation when the former is very low. Finally, we propose that a more risk‐averse partner will engage in fewer innovative activities as such a partner will be less sensitive to the pay‐for‐performance clause.
Telemedicine for the acute management of stroke in Burgundy, France: an evaluation of effectiveness and safety
Authors: Legris N. , Hervieu‐Bègue M. , Daubail B. , Daumas A. , Delpont B. , Osseby G.‐V. , Rouaud O. , Giroud M. , Béjot Y.
Published: May 2016

Background

In the context of the development of telemedicine in France to address low thrombolysis rates and limited stroke infrastructures, a star‐shaped telestroke network was implemented in Burgundy (1.6 million inhabitants). We evaluated the safety and effectiveness of this network for thrombolysis in acute ischemic stroke patients.

Methods

One hundred and thirty‐two consecutive patients who received intravenous thrombolysis during a telemedicine procedure (2012–2014) and 222 consecutive patients who were treated at the stroke center of Dijon University Hospital, France (2011–2012) were included. Main outcomes were the modified Rankin scale (mRS) score and case fatality at 3 months. Comparisons between groups were made using multivariable ordinal logistic regression and logistic regression analyses, respectively.

Results

Baseline characteristics of telethrombolysis patients were similar to those of patients undergoing thrombolysis locally except for a higher frequency of previous cancer and pre‐morbid handicap, and a trend towards greater severity at admission in the former. The distribution of mRS scores at 3 months was similar between groups, as were case‐fatality rates (18.9% in the telethrombolysis group versus 16.5%, P = 0.56). In multivariable models, telethrombolysis did not independently influence functional outcomes at 3 months (odds ratio for a shift towards a worse outcome on the mRS, 1.11; 95% confidence interval, 0.74–1.66, P = 0.62) or death (odds ratio, 0.86; 95% confidence interval, 0.44–1.69, P = 0.66).

Conclusion

The implementation of a regional telemedicine network for the management of acute ischemic stroke appeared to be effective and safe. Thanks to this network, the proportion of patients who benefit from thrombolysis will increase. Further research is needed to evaluate economic benefits.
Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline
Authors: Knol Anne C. , Vallée Audrey , Herbreteau Guillaume , Nguyen Jean‐Michel , Varey Emilie , Gaultier Aurélie , Théoleyre Sandrine , Saint‐Jean Mélanie , Peuvrel Lucie , Brocard Anabelle , Quéreux Gaëlle , Khammari Amir , Denis Marc G. , Dréno Brigitte
Published: May 2016

Circulating tumor DNA is a promising non‐invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty‐eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification‐refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment.
Effects of mammalian target of rapamycin inhibitors on cytokine production and differentiation in keratinocytes
Authors: DeTemple Viola , Satzger Imke , Walter Antje , Schaper Katrin , Gutzmer Ralf
Published: May 2016

Risk factors for the development of cutaneous squamous cell carcinoma (cSCC) include ultraviolet radiation and immunosuppression. In particular, solid organ transplant recipients show a high incidence of cSCC, depending on the immunosuppressive regimen. While azathioprine or calcineurin inhibitors increase the risk of cSCC development, mammalian target of rapamycin (mTOR) inhibitors decreases this risk. At the moment, the mechanisms behind this protective effect of mTOR inhibitors are not fully understood. We evaluated effects of the mTOR inhibitors sirolimus and everolimus on keratinocytes, cSCC cell lines and an organotypic skin model in vitro in regard to proliferation, cytokine secretion and differentiation. We show that mTOR inhibitors block keratinocyte proliferation and alter cytokine and cytokeratin production: in particular, mTOR inhibition leads to upregulation of interleukin‐6 and downregulation of cytokeratin 10. Therefore, mTOR inhibitors have effects on keratinocytes, which could play a role in the pathogenesis of cSCC.
Can people change the ecological rules that appear general across space?
Authors: Šizling A. L. , Pokorný P. , Juřičková L. , Horáčková J. , Abraham V. , Šizlingová E. , Ložek V. , Tjørve E. , Tjørve K. M. C. , Kunin W.
Published: May 2016

Aim

Projections of human impact on the environment and biodiversity patterns are crucial if we are to prevent their destruction. Such projections usually involve the assumption that the same human activities always affect biodiversity in the same way, either in geographically distant areas within the same time‐scale or in the same areas in different periods. In this paper, plant and snail fossils from central Europe that cover the last 12,000 years provide evidence against this assumption.

Location

Central Europe.

Methods

We examined fossil data on central European plants and snails and extracted time‐series of (1) local species richness (alpha diversity) at a scale of approximately 300 m × 300 m and decays of (2) the Jaccard index and (3) Simpson's beta with increasing distance (up to approximately 400 km) through time.

Results

We show that two vital biodiversity patterns follow neither oxygen‐isotope nor borehole temperature proxies, but instead vary between archaeologically known periods, with the most noticeable and irreversible breaks (1) when arable agriculture was introduced into central Europe, (2) when the Roman Empire collapsed, and (3) during the event known as the 12th‐century colonization in central Europe. The patterns computed from data across time sometimes contradicted the patterns computed across space.

Main conclusions

We therefore infer that people can, and sometimes have, contributed to temporal changes in ecological rules that are seemingly general across space. Our findings indicate that the changes in ecological rules are so substantial that efforts to project future biodiversity based on space‐for‐time substitution might fail, unless we gain knowledge about how these general rules are altered.