bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Preconception Substance Use Associated With Unplanned or Poorly Timed Pregnancy?
Authors: Lundsberg Lisbet S. , Peglow Stephanie , Qasba Neena , Yonkers Kimberly A. , Gariepy Aileen M.
Published: March 2018

Objective:

Unplanned and poorly timed pregnancies are associated with adverse maternal and neonatal outcomes. Further understanding of preconception substance use with unplanned and poorly timed pregnancy is warranted.

Methods:

Data were analyzed from a prospective study enrolling women early in pregnancy. Preconception tobacco, alcohol, marijuana, opioid, and cocaine use was ascertained. Participants reported whether their current pregnancy was planned and whether it was a good time to be pregnant. Multivariable logistic regression modeling generated risk estimates for preconception substance use, and pregnancy planning and timing, adjusting for confounders.

Results:

Overall, 37.2% reported unplanned pregnancy, 13.0% poorly timed pregnancy, and 39.0% reported either unplanned and/or poorly timed pregnancy. Within 6 months preconception, one-fifth (20.2%) reported nicotine cigarette use. In the month before conception, 71.8% reported alcohol use, 6.5% marijuana, and approximately 1% opioid or cocaine use. Multivariable analysis demonstrated preconception opioid use was associated with increased odds of poorly timed pregnancy (odds ratio [OR] 2.87, 95% confidence interval [CI] 1.03–7.99). Binge drinking the month before conception was associated with increased odds of poorly timed pregnancy and unplanned pregnancy (OR 1.75, 95% CI 1.01–3.05; and OR 1.68, 95% CI 1.01–2.79, respectively). Marijuana use 2 to 3 times in the month preconception was associated with increased risk of unplanned pregnancy, and unplanned and/or poorly timed pregnancy compared with nonuse (OR 1.78, 95% CI 1.03–3.08; and OR 1.79, 95% CI 1.01–3.17, respectively). Preconception tobacco or cocaine use was not associated with unplanned or poorly timed pregnancy following adjustment.

Conclusions:

We demonstrate increased odds of unplanned or poorly timed pregnancy among women with preconception binge drinking, marijuana use, and opioid use; however, no association is observed with other substances after multivariable adjustment, including tobacco. Further research to evaluate high-level preconception substance use and substance disorders with pregnancy planning and timing is warranted. Focused efforts optimizing preconception health behaviors and reducing risk of unplanned or poorly timed pregnancy are needed.
Tocilizumab in Giant Cell Arteritis
Authors: Mariano Vincent J. , Frishman William H.
Published: March 2018

Giant cell arteritis is a granulomatous immune-mediated vasculitis of medium and large vessels. It most commonly affects white females over the age of 50 and is the most common primary vasculitis in the United States. Treatment of this disease has classically been with high-dose corticosteroids, but this therapy has been associated with severe morbidity and mortality. Tocilizumab, a humanized monoclonal antibody targeting the interleukin-6 receptor, has been used with great efficacy and safety in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis. As interleukin-6 has been shown to be a key cytokine in giant cell arteritis, the use of an inhibiting agent has been explored. In the 15 case reports/series that were reviewed, most patients were given tocilizumab due to refractory giant cell arteritis and/or intolerance to glucocorticoid therapy, and most experienced remission of symptoms. At this time, there are only 2 randomized control trials to evaluate the efficacy and safety of tocilizumab use in giant cell arteritis. The phase II trial by Villiger et al and the GiACTA trial both showed that tocilizumab greatly increased the rate of sustained remission in giant cell arteritis over the course of 1 year. The most common adverse events were similar to those seen with use in rheumatoid arthritis: infections, neutropenia, and increases in lipids and liver function test enzymes. Based on the results of numerous case studies and the 2 randomized control trials, tocilizumab is the first agent to be approved by the Food and Drug Administration for treatment of giant cell arteritis.
Diagnostic Abilities of the Optical Microangiography Parameters of the 3×3 mm and 6×6 mm Macular Scans in Glaucoma
Authors: Rao Harsha L. , Riyazuddin Mohammed , Dasari Srilakshmi , Puttaiah Narendra K. , Pradhan Zia S. , Weinreb Robert N. , Mansouri Kaweh , Webers Carroll A.B.
Published: March 2018

Purpose:

To evaluate the diagnostic abilities of macular vessel length and perfusion densities measured with optical microangiography (OMAG) over a 3×3 mm and a 6×6 mm region, and to compare these with macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with primary open-angle glaucoma (POAG).

Methods:

In a cross-sectional study, 96 eyes of 57 control subjects and 88 eyes of 57 POAG patients underwent macular imaging with optical coherence tomography. Area under receiver operating characteristic curves (AUC) and sensitivities at 90% specificity of OMAG and GCIPL parameters were evaluated.

Results:

Most OMAG parameters of the 3×3 mm macular scan and all inner sector parameters of the 6×6 mm scan were similar (P>0.05) in the POAG and control eyes. All outer sector OMAG parameters of the 6×6 mm scan were significantly less (P<0.05) in the POAG eyes. AUC and sensitivity at 90% specificity of the best parameter of the 3×3 mm OMAG scan (inner temporal vessel length density; 0.65% and 26%, respectively) were statistically similar (P>0.05) to that of the 6×6 mm scan (outer inferior vessel length density; 0.72% and 30%, respectively). AUC and sensitivity of the best GCIPL thickness parameter (inferotemporal GCIPL thickness, 0.84% and 67%) were significantly better (P<0.05) than that of the vessel length densities.

Conclusions:

The outer sector measurements of the 6×6 mm macular OMAG scans seem to be better than the inner sector measurements in diagnosing glaucoma. The GCIPL thickness measurements were significantly better than all macular OMAG parameters in diagnosing glaucoma.
Preterm Children Have Higher Risk Than Full-term Children of Invasive Pneumococcal Disease During the First 2 Years of Life
Authors: Riise Øystein Rolandsen , Laake Ida , Vestrheim Didrik , Winje Brita Askeland , Moster Dag , Storsæter Jann
Published: March 2018

Background:

A few previous studies have reported an increased risk of invasive pneumococcal disease (IPD) in children born preterm, but this has not been investigated in a cohort study. The impact of 7-valent pneumococcal conjugate vaccine (PCV7) on IPD incidence rates in preterm children is unknown.

Methods:

Data from the Medical Birth Registry of Norway (2002–2010) were linked to other national registries. In total, 628,138 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression.

Results:

We identified 411 cases of IPD. We observed higher rates of IPD in preterm than in full-term children for the intervals 0–23, 0–5 and 6–23 months of age, IRRs = 1.83 (95 % CI: 1.36–2.47), 2.95 (95% CI: 1.44–6.06) and 1.69 (95% CI: 1.22–2.34), respectively. The risk for IPD was reduced in the PCV7-period (2007–2010) compared with that of the pre PCV7-period (2002–2005) for children 6–23 months of age, IRRs = 0.20 (95% CI: 0.08–0.53) for preterm children and 0.28 (95% CI: 0.21–0.38) for full-term children, but not for those 0–5 months of age, IRRs = 1.94 (95% CI: 0.48–7.80) and 0.71 (95% CI: 0.38–1.33).

Conclusions:

Preterm children had an increased risk of IPD. After introduction of PCV7, the rate of IPD was reduced among preterm and full-term children from 6 months of age.
Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection
Authors: Yakoot Mostafa , El‐Shabrawi Mortada H. , AbdElgawad Manal M. , Mahfouz Aml A. , Helmy Sherine , Abdo Alaa M. , El‐Khayat Hisham R.
Published: March 2018

Objectives:

Dual sofosbuvir/daclatasvir (SOF/DCV) therapy is currently recommended by the European Association for Study of Liver (EASL) as an option for the treatment of chronic hepatitis C virus (HCV) infection in adults for all genotypes; however, it is still not considered for patients younger than 18 years old. We aimed to test safety and efficacy of SOF/DCV in adolescent patients 12 to 17 years old with chronic HCV, genotype 4 infection.

Methods:

We conducted a prospective, uncontrolled, open‐label multicenter study. A total of 30 chronic HCV‐infected adolescents, aged from 12 to 17 years old were included and treated with dual SOF/DCV for 12 weeks. Patients were monitored throughout the treatment and follow‐up period for safety and efficacy outcome measures including the sustained virologic response 12 (SVR12) rate.

Results:

The intention‐to‐treat (ITT) SVR12 rate was 29 of 30 (96.7%; 95% confidence interval [CI] 83.3%–99.4%). The only patient who did not achieve SVR12 was lost to follow‐up after showing viral negativity at the end of treatment (EOT) visit. Whereas all the remaining 29 patients (100%, 95% CI 88.3%–100%) who completed the follow‐up visits achieved SVR12. All patients showed normalized liver enzymes with normal hematological, liver and renal function tests at the end of the study. No fatalities or treatment‐emergent serious or severe adverse events were reported throughout the study.

Conclusions:

SOF/DCV combined therapy could be a safe and effective treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4 infection. (See Video, Supplemental Digital Content, http://links.lww.com/MPG/B348).
Carolina Care at University of North Carolina Health Care
Authors: Tonges Mary , Ray Joel D. , Herman Suzanne , McCann Meghan
Published: March 2018

Patient satisfaction is a key component of healthcare organizations' performance. Providing a consistent, positive patient experience across a system can be challenging. This article describes an organization's approach to achieving this goal by implementing a successful model developed at the flagship academic healthcare center across an 8-hospital system. The Carolina Care at University of North Carolina Health Care initiative has resulted in substantive qualitative and quantitative benefits including higher patient experience scores for both overall rating and nurse communication.
Skin Laceration in Collagenase Clostridium histolyticum Treatment for Dupuytren's Contracture
Authors: Sanjuan-Cervero Rafael , Carrera-Hueso Francisco J. , Oliver-Mengual Salvador , Ramon-Barrios Maria A. , Peimer Clayton A. , Fikri-Benbrahim Narjis
Published: March 2018

BACKGROUND:

Dupuytren's contracture produces a progressive flexion contracture of the affected fingers. Collagenase Clostridium histolyticum produces breakdown of the cord in the hand and/or finger(s) that tightens as a result of the disease creating a contracture, allowing manual traction and cord rupture. One of the side effects is spontaneous skin laceration when the finger is extended.

OBJECTIVES:

To evaluate the development of skin lacerations in Dupuytren's contracture treated with collagenase Clostridium histolyticum, to determine predisposing factors, and evaluate the effectiveness of 2 different treatments (antiseptic and non–antiseptic dressings).

PARTICIPANTS:

Included 157 patients diagnosed with Dupuytren's contracture and treated with collagenase Clostridium histolyticum.

METHODS:

Analysis of variables and logistic regression model were applied to determine their possible relationship with skin lacerations. The effectiveness of the type of treatment used was evaluated by comparing the amount of time required for healing.

RESULTS:

Skin lacerations were present in 33.1% (n = 52) of patients, with an average laceration length of 1.12 (SD: 0.70) cm. Characteristics that were significant predisposing factors for lacerations were disease bilateralism (p = .002), previous surgical intervention (p = .003), and initial matacarpophalangeal joint contracture (p < .001). Worse initial contracture (Z = 5.94; p < .001) had a greater risk of laceration as did those who had prior hand surgery, or whose little finger was affected. Average treatment length of healing was 11.24 days (SD: 8.13). All wounds healed successfully. There were no significant differences (p = .511) in healing between different dressings evaluated.

CONCLUSIONS:

Skin lacerations as a consequence of treating Dupuytren's contracture with collagenase Clostridium histolyticum occur often and are moderately serious. For all cases, evolution is satisfactory in less than 2 weeks, and the type of treatment does not appear to make any difference in healing time.
Postmortem Cholesterol Levels in Peripheral Nerve Tissue
Authors: Vacchiano Giuseppe , Luna Maldonado Aurelio , Matas Ros Maria , Fiorenza Elisa , Silvestre Angela , Simonetti Biagio , Pieri Maria
Published: March 2018

The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times—from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right(R2= 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left(R2= 0.794) for the left wrist.

At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.
Obesity blocks oligodendrocyte precursor cell differentiation and impedes repair after white matter stroke
Authors: Xiao Guanxi , Burguet Jasmine , Kawaguchi Riki , Havton Leif A. , Hinman Jason D.
Published: March 2018

Obesity is a growing public health problem that increases rates of white matter atrophy and increases the likelihood of ischemic lesions within white matter. However, the cellular and molecular mechanisms that regulate these changes are unknown. We hypothesized that obesity may alter oligodendrocytes and myelin priming white matter for worsening injury and repair responses after ischemia. C57Bl/6 mice fed a high fat diet (60% kcal from fat) show increased numbers of oligodendrocyte precursor cells (OPCs), decreased myelin thickness with elevated g-ratios, and shorter paranodal axonal segments, indicating accelerated myelin turnover. Fate mapping of OPCs inPDGFRα-CreERT;Rpl22tm1.1Psammice demonstrated that OPC differentiation rates are enhanced by obesity. Gene expression analyses using a novel oligodendrocyte staging assay demonstrated OPC differentiation is blocked by obesity in between the pre-myelinating and myelinating stage. Using a model of subcortical white matter stroke, the number of stroke-responsive OPCs in obese mice was increased after stroke. At early time points after ischemic white matter stroke, spatial mapping of stroke-responsive OPCs indicates that obesity leads to increased OPCs at the edge of ischemic white matter lesions. At later time points, obesity results in increased OPCs within the ischemic lesion while reducing the number of GST-π-positive mature oligodendrocytes in the lesion core. These data indicate that obesity disrupts normal white matter biology by blocking oligodendrocyte differentiation, leads to an exaggerated response of OPCs to white matter ischemia, and limits remyelination after stroke.

Significance Statement

Obesity is a growing public health crisis that specifically increases the development of white matter lesions and silent brain infarcts. This relationship implies a direct cellular effect on white matter yet direct evidence is limited. We modeled diet-induced obesity in mice and studied the effect on oligodendrocyte biology and the response to focal white matter stroke. Adult-onset obesity results in thinner myelin, compromised axonal microdomain structure, and blocks the differentiation of OPCs, leaving the white matter with increased numbers of OPCs. After focal white matter stroke in obese mice, the early OPC response to stroke is exaggerated while late reparative OPC differentiation is blocked. These results suggest that obesity specifically blocks OPC differentiation with consequence on brain repair after stroke.
A naturally-occurring dominant-negative competitor of Keap1 against its inhibition of Nrf2
Authors: Qiu Lu , Wang Meng , Zhu Yuping , Xiang Yuancai , Zhang Yiguo
Published: March 2018

Transcription factor Nrf2 is a master regulator of antioxidant and/or electrophile response elements (AREs/EpREs)driven genes involved in homeostasis, detoxification and adaptation to various stresses. The cytoprotective activity of Nrf2, though being oppositely involved in both cancer prevention and progression, is critically controlled by Keap1 (Kelch-like ECH-associated protein 1) as an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, that is a key sensor for oxidative and electrophilic stresses. Now, we first report a novel naturally-occurring mutant of Keap1, designated Keap1ΔC, which lacks most of its C-terminal Nrf2-interacting domain essential for inhibition of the CNC-bZIP factor. This mutant Keap1ΔC is yielded by translation from an alternatively mRNA-spliced variant lacking the fourth and fifth exons, but their coding sequences are retained in the wild-type Keap1 locus (with no genomic deletions). Although this variant was found primarily in the human highly-metastatic hepatoma (MHCC97H) cells, it was widely expressed at very lower levels in all other cell lines examined. No matter whether Keap1ΔC retains less or no ability to inhibit Nrf2, it functions as a dominant-negative competitor of Keap1 against its inhibition of Nrf2-target genes. This is due to its antagonist effect on Keap1-mediated turnover of Nrf2 protein.
Cross-species functional modules link proteostasis to human normal aging
Authors: Komljenovic Andrea , Li Hao , Sorrentino Vincenzo , Kutalik Zoltán , Auwerx Johan , Robinson-Rechavi Marc
Published: March 2018

The evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan, such as caloric restriction, suggests that aging-related research in model organisms is directly relevant to human aging. Since human lifespan is a complex trait, a systems-level approach will contribute to a more comprehensive understanding of the underlying aging landscape. Here, we integrate evolutionary and functional information of normal aging across human and model organisms at three levels: gene-level, process-level, and network-level. We identify evolutionarily conserved modules of normal aging across diverse taxa, and importantly, we show that proteostasis involvement is conserved in healthy aging. Additionally, we find that mechanisms related to protein quality control network are enriched in 22 age-related genome-wide association studies (GWAS) and are associated to caloric restriction. These results demonstrate that a systems-level approach, combined with evolutionary conservation, allows the detection of candidate aging genes and pathways relevant to human normal aging.

Highlights

Normal aging is evolutionarily conserved at the module level.

Core pathways in healthy aging are related to mechanisms of protein quality network

The evolutionarily conserved pathways of healthy aging react to caloric restriction.

Our integrative approach identifies evolutionarily conserved functional modules and showed enrichment in several age-related GWAS studies.
Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia
Authors: Curtis David
Published: March 2018

Background

The polygenic risk score (PRS) for schizophrenia, derived from very large numbers of weakly associated genetic markers, has been repeatedly shown to be robustly associated with schizophrenia in independent samples and also with other diseases and traits.

Aims

To explore the distribution of the schizophrenia PRS in subjects of different ancestry.

Method

The schizophrenia PRS derived from the large genome-wide association study carried out by the Psychiatric Genetics Consortium was calculated using the downloaded genotypes of HapMap subjects from eleven different ancestral groups. It was also calculated using downloaded genotypes of European schizophrenia cases and controls from the CommonMind Consortium.

Results

The PRS for schizophrenia varied significantly between ancestral groups (p < 2*10−16) and was much higher in African than European HapMap subjects. The mean difference between these groups was ten times as high as the mean difference between European schizophrenia cases and controls. The distributions of scores for African and European subjects hardly overlapped.

Conclusions

The PRS cannot be regarded as simply a measure of the polygenic contribution to risk of schizophrenia and clearly contains a strong ancestry component. It is possible that this could be controlled for to some extent by incorporating principal components as covariates but doubts remain as to how it should be interpreted. The PRS derived from European subjects cannot be applied to non-Europeans, limiting its potential usefulness and raising issues of inequity. Previous studies which have used the PRS should be re-examined in the light of these findings.

Declaration of interest

The author declares he has no conflict of interest.
On the synchronized failure of global crop production
Authors: Mehrabi Zia , Ramankutty Navin
Published: March 2018

Multiple breadbasket failure is a risk to global food security. However, there are no global analyses that have assessed if global food production has actually tended towards synchronized failure historically. We show that synchronization in production for major commodities such as maize and soy has declined in recent decades, but that increased synchrony, when present, has had marked destabilizing effects. Under the hypothetical case of a synchronized failure event, we estimate simultaneous global production losses for rice, wheat, soy and maize between −18% and −36%. Our results show that maintaining asynchrony in the food system and mitigating instability through food storage in good years, both require a central place in discussions of future food demand under mean climate change, population growth and consumption trends.
Ldb1 mediates trans enhancement in mammals
Authors: Monahan K. , Horta A. , Mumbay-Wafula A.M. , Li L. , Zhao Y. , Love P.E. , Lomvardas S.
Published: March 2018

Singular olfactory receptor (OR) gene expression1,2 coincides with the formation of a multi-chromosomal enhancer hub that associates with the only transcribed OR allele in each cell3,4. This hub consists of converging transcriptional enhancers3, or “Greek Islands”, defined by stereotypic binding of Lhx2 and Ebf on a shared, composite DNA motif5. How this multi-chromosomal hub, or any other genomic compartment, assembles is unknown, and so is the significance of compartmentalization in transcription. Here, we report that LIM domain binding protein 1 (Ldb1), which is recruited by Lhx2 and Ebf to Greek Islands, promotes robust and specific trans interactions between these enhancers. In addition to disrupting Greek Island hubs, Ldb1 deletion also causes significant downregulation of OR transcription. Thus, our data provide insight to the formation of genomic compartments, confirm the essential role of interchromosomal interactions in OR gene choice, and establish trans enhancement as a mechanism for mammalian gene activation.
Tuning gene expression variability and multi-gene regulation by dynamic transcription factor control
Authors: Benzinger Dirk , Khammash Mustafa
Published: March 2018

Many natural transcription factors are regulated in a pulsatile fashion, but it remains unknown whether synthetic gene expression systems can benefit from such dynamic regulation. Using a fast-acting, light-responsive transcription factor inSaccharomyces cerevisiae, we show that dynamic pulsatile signals reduce cell-to-cell variability in gene expression. We then show that by encoding such signals into a single input, expression mean and variability can be precisely and independently tuned. Further, we construct a light-responsive promoter library and demonstrate how pulsatile signaling also enables graded multi-gene regulation at fixed expression ratios, despite differences in promoter dose-response characteristics. Pulsatile regulation can thus lead to highly beneficial functional behaviors in synthetic biological systems, which previously required laborious optimization of genetic parts or complex construction of synthetic gene networks.
An unexpected contribution of lincRNA splicing to enhancer function
Authors: Tan Jennifer Y. , Biasini Adriano , Young Robert S. , Marques Ana C.
Published: March 2018

Transcription is common at active mammalian enhancers sometimes giving rise to stable and unidirectionally transcribed enhancer-associated long intergenic noncoding RNAs (elincRNAs). ElincRNA expression is associated with changes in neighboring gene product abundance and local chromosomal topology, suggesting that transcription at these loci contributes to gene expression regulation in cis. Despite the lack of evidence supporting sequence-dependent functions for most elincRNAs, splicing of these transcripts is unexpectedly common. Whether elincRNA splicing is a mere consequence of their cognate enhancer activity or if it directly impacts enhancer-associated cis-regulation remains unanswered.

Here we show that elincRNAs are efficiently and rapidly spliced and that their processing rate is strongly associated with their cognate enhancer activity. This association is supported by: their enrichment in enhancer-specific chromatin signatures; elevated binding of co-transcriptional regulators, including CBP and p300; increased local intra-chromosomal DNA contacts; and strengthened cis-regulation on target gene expression. Using nucleotide polymorphisms at elincRNA splice sites, we found that elincRNA splicing enhances their transcription and directly impacts cis-regulatory function of their cognate enhancers. Importantly, up to 90% of human elincRNAs have nucleotide variants that are associated with both their splicing and the expression levels of their proximal genes.

Our results highlight an unexpected contribution of elincRNA splicing to enhancer function.
Social communication between microbes colonizing the social honey bee Apis mellifera
Authors: Miller K.I. , Franklin C.D. , Mattila H. R. , Newton I.L.G.
Published: March 2018

The European honey bee (Apis mellifera) is a charismatic species that plays a critical role in the pollination of agriculturally important crops and native flora. One emerging field of research is that of the host-associated honey bee microbiome: a group of bacterial phylotypes consistently found within the honey bee, which may play critical roles such as protection from pathogens and nutrient acquisition. In other model systems, host-associated microbial communities are known to participate in a form of bacterial communication known as quorum sensing. This type of communication allows bacteria to sense their environment and respond with changes in gene expression, controlling a number of factors including virulence, biofilm formation, and cell motility. Here, we have investigated the production of a specific quorum sensing molecule by honey bee microbes in vivo and in vitro. We specifically focused on the inter-species signaling molecule, autoinducer-2 (AI-2). We identified the production of AI-2 by both the entire community (using honey bee gut homogenates) and by cultured isolates, using a Vibrio harveyi biosensor. By comparing newly emerged and adult bees, we showed this signal is likely coming from the core microbial community. Finally, using honey bee specific bacterial isolates, we identified changes in biofilm production when isolates are exposed to increased levels of exogenous AI-2. Altogether, these data provide multiple lines of evidence for the presence of quorum sensing inside the honey bee host. The effect of AI-2 on biofilm formation by honey bee specific bacteria identifies one potential avenue for quorum sensing to affect host health.

Author summary

Microbial communities associate with every animal on the planet and can have dramatic effects on the health of their host. The honey bee is one such animal, home to a characteristic community of bacteria, which may provide various benefits. Here, we show that these microbes are producing quorum sensing molecules which could support interactions between bacterial members and facilitate host colonization.
Clock-dependent chromatin topology modulates circadian transcription and behavior
Authors: Mermet Jérôme , Yeung Jake , Hurni Clémence , Mauvoisin Daniel , Gustafson Kyle , Jouffe Céline , Nicolas Damien , Emmenegger Yann , Gobet Cédric , Franken Paul , Gachon Frédéric , Naef Félix
Published: March 2018

The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms in behavior and physiology. Several studies have shown the possible roles of transcription factors and chromatin marks in controlling cyclic gene expression. However, how daily active enhancers modulate rhythmic gene transcription in mammalian tissues is not known. Using circular chromosome conformation capture (4C) combined with sequencing (4C-seq), we discovered oscillatory promoter–enhancer interactions along the 24-h cycle in the mouse liver and kidney. Rhythms in chromatin interactions were abolished in arrhythmic Bmal1 knockout mice. Deleting a contacted intronic enhancer element in the Cryptochrome 1 (Cry1) gene was sufficient to compromise the rhythmic chromatin contacts in tissues. Moreover, the deletion reduced the daily dynamics of Cry1 transcriptional burst frequency and, remarkably, shortened the circadian period of locomotor activity rhythms. Our results establish oscillating and clock-controlled promoter–enhancer looping as a regulatory layer underlying circadian transcription and behavior.
Supply chain drivers, partnerships and performance of high-tech SMEs
Authors: Rezaei Jafar , Ortt Roland , Trott Paul
Published: March 2018

Purpose

The purpose of this paper is to examine high-tech small-to-medium-sized enterprises (SMEs) supply chain partnerships. Partnerships are considered at the level of business function rather than the entire organisation. Second, the drivers of SMEs to engage in partnerships are assessed to see whether functions engage in partnerships for different reasons. Third, performance per function is assessed to see the differential effect of partnerships on the function’s performance.

Design/methodology/approach

In this study, the relationship between the drivers of SMEs to engage in partnerships, four types of partnerships (marketing and sales, research and development (R&D), purchasing and logistics, and production) and four types of functional performances of firms (marketing and sales, R&D, purchasing and logistics, and production) are examined. The data have been collected from 279 SMEs. The proposed hypotheses are tested using structural equation modelling.

Findings

The results indicate that there are considerable differences between business functions in terms of the degree of involvement in partnerships and the effect of partnerships on the performance of these functions. This paper contributes to research by explaining the contradictory results of partnerships on SMEs performance.

Practical implications

This study helps firms understand which type of partnership should be established based on the firm’s drivers to engage in supply chain partnership; and which partnership has a significant effect on which type of business performance of the firm.

Originality/value

The originality of this study is to investigate the relationship between different drivers to engage in supply chain partnership and different types of partnerships and different functional performance of firm in a single model.
Perception and barriers: reporting female genital mutilation
Authors: Gangoli Geetanjali , Gill Aisha , Mulvihill Natasha , Hester Marianne
Published: March 2018

Purpose

The purpose of this paper is to explore the perceptions of and barriers to reporting female genital mutilation (FGM) by victims and survivors of FGM to the police in England and Wales.

Design/methodology/approach

The paper is based on 14 interviews conducted with adult survivors and victims of FGM. A combination of 1:1 and group interviews were used, based on the preference of the respondents. Respondents were recruited in collaboration with specialist non-governmental organisations and major stakeholders in the area of honour-based violence and black and minority ethnic communities.

Findings

A key finding in this research was that all victims/survivors the authors interviewed stated that they did not support the practice of FGM, and that they would not follow it for younger women in their own family. Second, the authors found that none of the respondents had reported their experience to the police. Third, they identified key barriers to reporting, which included: their belief that reporting their own experience would not serve any purpose because they had experienced FGM as children, and in another country; and that they did not feel able to report new incidents of FGM in the community because of a lack of trust in the police due to previous negative experiences. Finally, they believed that FGM could be prevented only by work within the community, and not through engagement with the criminal justice system.

Originality/value

This is, to our knowledge, one of the first papers that is based on victims and survivors’ perceptions that explores barriers to reporting cases of FGM to the police, and offers levers for change.
Application of the RAND‐UCLA Appropriateness Methodology to a Large Multidisciplinary Stakeholder Group Evaluating the Validity and Feasibility of Patient‐Centered Standards in Geriatric Surgery
Authors: Berian Julia R. , Baker Tracey L. , Rosenthal Ronnie A. , Coleman JoAnn , Finlayson Emily , Katlic Mark R. , Lagoo‐Deenadayalan Sandhya A. , Tang Victoria L. , Robinson Thomas N. , Ko Clifford Y. , Russell Marcia M.
Published: March 2018

Objectives

To explore (1) differences in validity and feasibility ratings for geriatric surgical standards across a diverse stakeholder group (surgeons vs. nonsurgeons, health care providers vs. nonproviders, including patient‐family, advocacy, and regulatory agencies); (2) whether three multidisciplinary discussion subgroups would reach similar conclusions.

Data Source/Study Setting

Primary data (ratings) were reported from 58 stakeholder organizations.

Study Design

An adaptation of the RAND‐UCLA Appropriateness Methodology (RAM) process was conducted in May 2016.

Data Collection/Extraction Methods

Stakeholders self‐administered ratings on paper, returned via mail (Round 1) and in‐person (Round 2).

Principal Findings

In Round 1, surgeons rated standards more critically (91.2 percent valid; 64.9 percent feasible) than nonsurgeons (100 percent valid; 87.0 percent feasible) but increased ratings in Round 2 (98.7 percent valid; 90.6 percent feasible), aligning with nonsurgeons (99.7 percent valid; 96.1 percent feasible). Three parallel subgroups rated validity at 96.8 percent (group 1), 100 percent (group 2), and 97.4 percent (group 3). Feasibility ratings were 76.9 percent (group 1), 96.1 percent (group 2), and 92.2 percent (group 3).

Conclusions

There are differences in validity and feasibility ratings by health professions, with surgeons rating standards more critically than nonsurgeons. However, three separate discussion subgroups rated a high proportion (96–100 percent) of standards as valid, indicating the RAM can be successfully applied to a large stakeholder group.
Using balanced acceptance sampling as a master sample for environmental surveys
Authors: van Dam‐Bates Paul , Gansell Oliver , Robertson Blair
Published: March 2018

Well‐designed environmental monitoring programmes for management organisations are important for evidence‐based decision making. However, many environmental problems are not single agency issues that require intervention or monitoring at one spatial scale. A master sample can be used to coordinate and scale monitoring designs to ensure consistency in information gathered and robustness of estimators at the different spatial scales.

We propose using balanced acceptance sampling (BAS) to generate a master sample. In this context, practical applications and justification of BAS as a master sample are addressed. These include sample generation, stratification, unequal probability sampling, rotating panel designs, and regional intensification. A method for incorporating legacy sites is also provided.

Using BAS as a master sample is conceptually simple, gives good spatial balance over different spatial scales, and is computationally efficient to generate. An example for terrestrial biodiversity monitoring in New Zealand is provided.

Environmental monitoring can benefit from increased coordination between agencies. A master sample is an excellent way to incorporate coordination directly into the sample design. BAS improves on methods previously described and provides an effective method to monitor populations at multiple spatial scales.
Inter‐disciplinary cooperation in a physician‐staffed emergency medical system
Authors: Reid B. O. , Rehn M. , Uleberg O. , Pleym L. E. N. , Krüger A. J.
Published: March 2018

Background

On‐scene management of pre‐hospital emergencies is often inter‐disciplinary, involving ground‐emergency medical services (EMS), police‐ and fire services, and in Norway general practitioners on‐call. This can also be supplemented by physician‐staffed EMS (P‐EMS), utilizing helicopters or rapid response vehicles. We hypothesized that P‐EMS cooperates extensively with other emergency services, and therefore the primary aim of this study was to investigate the fraction of inter‐disciplinary cooperation between P‐EMS and other emergency services.

Methods

Retrospective, observational study of primary pre‐hospital missions with patient contact performed at a Norwegian P‐EMS base from 01.01.06 to 31.12.15. Descriptive statistics, comparisons using Student`s t‐test, and chi‐squared test for trend were applied.

Results

Inter‐disciplinary cooperation occurred in 94.3% of the 8580 missions, of which physician‐staffed EMS cooperated with ground EMS in 92.4%, general practitioner 32.9%, police service 11.6% and fire service 11.8%. Trauma constituted 34.4 and cardiac arrest 14.1% of missions. The mean National Advisory Committee for Aeronautics score was 4.21 (95% Confidence Interval 4.18–4.24). There was an overall decrease in cooperation with general practitioners and the police service (P < 0.001). During helicopter missions, we reported a decrease in general practitioner cooperation compared to an increase during rapid response car missions (P < 0.001). In cardiac arrest cases, cooperation with both general practitioners and the fire service increased (P < 0.001).

Conclusion

Physician‐staffed EMS cooperates extensively with other professional emergency services, especially ground‐EMS. On‐scene cooperation with general practitioners decreased, whereas there was an increased cooperation with the fire service in a “first‐responder” role during cardiac arrest missions.
Xerostomia, salivary characteristics and gland volumes following intensity‐modulated radiotherapy for nasopharyngeal carcinoma: a two‐year follow up
Authors: Sim CPC , Soong YL , Pang EPP , Lim C , Walker GD , Manton DJ , Reynolds EC , Wee JTS
Published: March 2018

Background

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients.

Methods

Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre‐radiotherapy, mid‐radiotherapy, 2 weeks, 3 months and 2 years post‐radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed.

Results

Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post‐radiotherapy; volumes at 2 years post‐radiotherapy were 84% and 51% of pre‐radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post‐radiotherapy/pre‐radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post‐radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre‐radiotherapy levels.

Conclusions

Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation‐related oral diseases.
Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition
Authors: Davoli R. , Gaffo E. , Zappaterra M. , Bortoluzzi S. , Zambonelli P.
Published: March 2018

The identification of the molecular mechanisms regulating pathways associated with the potential for fat deposition in pigs can lead to the detection of key genes and markers for the genetic improvement of fat traits. Interactions of microRNAs (miRNAs) with target RNAs regulate gene expression and modulate pathway activation in cells and tissues. In pigs, miRNA discovery is far from saturation, and the knowledge of miRNA expression in backfat tissue and particularly of the impact of miRNA variations is still fragmentary. Using RNA‐seq, we characterized the small RNA (sRNA) expression profiles in Italian Large White pig backfat tissue. Comparing two groups of pigs divergent for backfat deposition, we detected 31 significant differentially expressed (DE) sRNAs: 14 up‐regulated (including ssc‐miR‐132, ssc‐miR‐146b, ssc‐miR‐221‐5p, ssc‐miR‐365‐5p and the moRNA ssc‐moR‐21‐5p) and 17 down‐regulated (including ssc‐miR‐136, ssc‐miR‐195, ssc‐miR‐199a‐5p and ssc‐miR‐335). To understand the biological impact of the observed miRNA expression variations, we used the expression correlation of DE miRNA target transcripts expressed in the same samples to define a regulatory network of 193 interactions between DE miRNAs and 40 DE target transcripts showing opposite expression profiles and being involved in specific pathways. Several miRNAs and mRNAs in the network were found to be expressed from backfat‐related pig QTL. These results are informative for the complex mechanisms influencing fat traits, shed light on a new aspect of the genetic regulation of fat deposition in pigs and facilitate the prospective implementation of innovative strategies of pig genetic improvement based on genomic markers.
A randomized clinical trial to evaluate the efficacy of contingency management for treatment of waterpipe tobacco addiction
Authors: Shishani Kawkab , Odom‐Maryon Tamara , Roll John M.
Published: March 2018

Background and Objectives

Unlike cigarette smoking cessation, waterpipe tobacco smoking cessation is relatively understudied. The objective of this randomized clinical trial was to examine the efficacy of contingency management (CM) for promoting initial waterpipe smoking abstinence.

Methods

The study used a two‐group, repeated measures design. Participants attended 10 visits (two visits per week, on Mondays and Thursdays) across 5 weeks. Thirty‐nine adult waterpipe tobacco users who did not smoke cigarettes and were not planning on quitting waterpipe tobacco smoking were randomly assigned to either the contingent (n = 19) or non‐contingent (n = 20) groups. Contingent group received monetary rewards based on negative salivary cotinine results. Earning rewards started at $14 and increased by $.50 with each subsequent negative sample for a maximum $192.50. Non‐contingent group earned rewards independent of salivary cotinine results. Prolonged abstinence was defined as having negative salivary cotinine results for eight or more visits (two lapses were allowed); and 7‐day point prevalence was defined as having negative salivary cotinine results at visit 9 and 10 (final week).

Results

The prolonged abstinence rate in the contingent and non‐contingent groups were 42.1% and 5.0%, respectively, (p = .008). The 7‐day point prevalence in the contingent and non‐contingent were 47.4% and 5.0%, respectively, (p = .003).

Discussion and Conclusions

Rewards contingent on biochemically verified abstinence promote initial waterpipe tobacco cessation. This is useful information for consideration in future cessation programs for waterpipe smokers.

Scientific Significance

CM strategy may have potential benefit in addressing waterpipe tobacco smoking in non‐treatment seeking adults. (Am J Addict 2018;27:202–209)
Medical students and midwives – How do they view each other?
Authors: Cheng Hon C. , de Costa Caroline , Woods Cindy
Published: March 2018

Medical students from James Cook University who had completed their rotation in obstetrics, and midwives working in Cairns Hospital who had undertaken supervision of medical students in the birth suite, were invited to complete anonymous questionnaires on their views of their respective roles in the birth suite. Several issues were identified including increased medical and midwifery student numbers, and lack of communication between midwives and medical students. Increased cooperation and communication between medical and midwifery education providers is urgently needed to improve both student groups’ learning experiences.
Physician characteristics influence the trends in resuscitation decisions at different ages
Authors: Hansen Thor Willy Ruud , Aasland Olaf , Janvier Annie , Førde Reidun
Published: March 2018

Aim

We examined how physicians in different medical specialties would evaluate treatment decisions for vulnerable patients in need of resuscitation.

Methods

A survey depicting six acutely ill patients from newborn infant to aged, all in need of resuscitation with similar prognoses, was distributed (in 2009) to a representative sample of 1650 members of the Norwegian Medical Association and 676 members of the Norwegian Pediatric Association.

Results

There were 1335 respondents (57% participation rate). The majority of respondents across all specialties thought resuscitation was in the best interest of a 24 weeks’ gestation preterm infant and would resuscitate the patient, but would also accept palliative care on the family's demand. Accepting a family's refusal of resuscitation was more common for the newborn infants. Specialists were overall similar in their answers, but specialty, age and gender were associated with different answers for the patients at both ends of the age spectrum.

Conclusion

Resuscitation decisions for the very young do not always seem to follow the best interest principle. Specialty and personal characteristics still have an impact on how we consider important ethical issues. We must be cognisant of our own valuations and how they may influence care.