bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus
Authors: Li Lian‐Ju , Zhu Zhi‐Wei , Zhao Wei , Tao Sha‐Sha , Li Bao‐Zhu , Xu Shu‐Zhen , Wang Jie‐Bing , Zhang Ming‐Yue , Wu Jun , Leng Rui‐Xue , Fan Yin‐Guang , Pan Hai‐Feng , Ye Dong‐Qing
Published: April 2018

Circular RNAs (circRNAs) represent a class of non‐coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down‐regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up‐regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin‐2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down‐regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa‐miR‐6127. Circular RNA–mRNA co‐expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin‐2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.
Improved transmittance and ferroelectric properties realized in KNN ceramics via SAN modification
Authors: Zhao Xumei , Chai Qizhen , Chen Bi , Chao Xiaolian , Yang Zupei
Published: April 2018

Transparent, Sr(Al0.5Nb0.5)O3‐modified K0.5Na0.5NbO3 (KNN) ceramics were successfully fabricated by a solid‐state pressureless sintering method in this work. The obtained microstructure, transmittance, and electrical properties were characterized in detail. Our results indicated that the modification by Sr(Al0.5Nb0.5)O3 significantly limited the grain growth behavior of KNN, resulting in dense ceramics with submicron grain size (<0.5 μm) and small pore size. Consequently, the ceramic with the 0.96K0.5Na0.5NbO3‐0.04Sr(Al0.5Nb0.5)O3 composition showed superior transmittance and electrical properties: T = 55% in the visible region (0.78 μm), d33 = 105 pC/N, εr = 1021, and Pr = 15.1 μC/cm2, which were significantly higher than those of pure KNN. Our findings implied that the addition of Sr(Al0.5Nb0.5)O3 could be a good strategy to obtain superior transmittance and electrical properties in KNN and may shed light on other ferroelectric systems.
Quality of life, anxiety, depression and burden among stroke caregivers: A longitudinal, observational multicentre study
Authors: Pucciarelli Gianluca , Ausili Davide , Galbussera Alessia Antonella , Rebora Paola , Savini Serenella , Simeone Silvio , Alvaro Rosaria , Vellone Ercole
Published: April 2018

Aim

To longitudinally describe stroke caregivers’ quality of life, anxiety, depression and burden and to identify predictors of stroke caregivers’ quality of life, anxiety, depression and burden.

Background

Caregivers have a key role in stroke survivor care and the first year of caregiving is the most challenging. To give tailored interventions, it is important to capture changes and identify predictors of caregiver quality of life, anxiety, depression and burden during the first year.

Design

A 12‐month longitudinal study. Data were collected between June 2013–May 2016.

Methods

Changes in stroke caregiver quality of life, anxiety and depression and burden and their predictors were identified using linear mixed‐effects models.

Results

The caregivers (N = 244) were 53 years old and mostly female. Caregiver quality of life did not change significantly over the 12 months, anxiety and depression decreased up to 9 months and caregiver burden decreased from baseline to 3 months, then increased up to 9 months. Higher caregiver quality of life was predicted by caregiver younger age, higher education, living with a stroke survivor, survivor older age and higher physical functioning; higher anxiety and depression were predicted by older caregiver age and younger survivor age; higher burden was predicted by caregiver male gender, the caregiver not living with survivor and survivor lower physical functioning.

Conclusion

The first 9 months of caregiving are particularly problematic for caregivers. The trajectories of the above variables and their predictors may be useful for policy makers, clinicians, investigators and educators to give better care to stroke caregivers and their survivors.
Global species delimitation and phylogeography of the circumtropical ‘sexy shrimp’ Thor amboinensis reveals a cryptic species complex and secondary contact in the Indo‐West Pacific
Authors: Titus Benjamin M. , Daly Marymegan , Hamilton Natalie , Berumen Michael L. , Baeza J. Antonio
Published: April 2018

Aim

The “sexy shrimp” Thor amboinensis is currently considered a single circumtropical species. However, the tropical oceans are partitioned by hard and soft barriers to dispersal, providing ample opportunity for allopatric speciation. Herein, we test the null hypothesis that T. amboinensis is a single global species, reconstruct its global biogeographical history, and comment on population‐level patterns throughout the Tropical Western Atlantic.

Location

Coral reefs in all tropical oceans.

Methods

Specimens of Thor amboinensis were obtained through field collection and museum holdings. We used one mitochondrial (COI) and two nuclear (NaK, enolase) gene fragments for global species delimitation and phylogenetic analyses (n = 83 individuals, 30 sample localities), while phylogeographical reconstruction in the TWA was based on COI only (n = 303 individuals, 10 sample localities).

Results

We found evidence for at least five cryptic lineages (9%–22% COI pairwise sequence divergence): four in the Indo‐West Pacific and one in the Tropical Western Atlantic. Phylogenetic reconstruction revealed that endemic lineages from Japan and the South Central Pacific are more closely related to the Tropical Western Atlantic lineage than to a co‐occurring lineage that is widespread throughout the Indo‐West Pacific. Concatenated and species tree phylogenetic analyses differ in the placement of an endemic Red Sea lineage and suggest alternate dispersal pathways into the Atlantic. Phylogeographical reconstruction throughout the Tropical Western Atlantic reveals little genetic structure over more than 3,000 km.

Main conclusions

Thor amboinensis is a species complex that has undergone a series of allopatric speciation events and whose members are in secondary contact in the Indo‐West Pacific. Nuclear‐ and mitochondrial‐ gene phylogenies show evidence of introgression between lineages inferred to have been separated more than 20 Ma. Phylogenetic discordance between multi‐locus analyses suggest that T. amboinensis originated in the Tethys sea and dispersed into the Atlantic and Indo‐West Pacific through the Tethys seaway or, alternatively, originated in the Indo‐West Pacific and dispersed into the Atlantic around South Africa. Population‐level patterns in the Caribbean indicate extensive gene flow across the region.
Localization of ventricular activation origin using patient‐specific geometry: Preliminary results
Authors: Zhou Shijie , Sapp John L. , AbdelWahab Amir , Šťovíček Petr , Horáček B. Milan
Published: April 2018

Background and objectives

Catheter ablation of ventricular tachycardia (VT) may include induction of VT and localization of VT‐exit site. Our aim was to assess localization performance of a novel statistical pace‐mapping method and compare it with performance of an electrocardiographic inverse solution.

Methods

Seven patients undergoing ablation of VT (4 with epicardial, 3 with endocardial exit) aided by electroanatomic mapping underwent intraprocedural 120‐lead body‐surface potential mapping (BSPM). Two approaches to localization of activation origin were tested: (1) A statistical method, based on multiple linear regression (MLR), which required only the conventional 12‐lead ECG for a sufficient number of pacing sites with known origin together with patient‐specific geometry of the endocardial/epicardial surface obtained by electroanatomic mapping; and (2) a classical deterministic inverse solution for recovering heart‐surface potentials, which required BSPM and patient‐specific geometry of the heart and torso obtained via computed tomography (CT).

Results

For the MLR method, at least 10–15 pacing sites with known coordinates, together with their corresponding 12‐lead ECGs, were required to derive reliable patient‐specific regression equations, which then enabled accurate localization of ventricular activation with unknown origin. For 4 patients who underwent epicardial mapping, the median of localization error for the MLR was significantly lower than that for the inverse solution (10.6 vs. 27.3 mm, P  =  0.034); a similar result held for 3 patients who underwent endocardial mapping (7.7 vs. 17.1 mm, P  =  0.017). The pooled localization error for all epicardial and endocardial sites was also significantly smaller for the MLR compared with the inverse solution (P  =  0.005).

Conclusions

The novel pace‐mapping approach to localizing the origin of ventricular activation offers an easily implementable supplement and/or alternative to the preprocedure inverse solution; its simplicity makes it suitable for real‐time applications during clinical catheter‐ablation procedures.
The responses of the inflammatory marker, pentraxin 3, to dietary sodium and potassium interventions
Authors: Hu Jia‐Wen , Wang Yang , Chu Chao , Wang KeKe , Yan Yu , Zheng Wenling , Ma Qiong , Mu Jian‐Jun
Published: April 2018

Pentraxin‐3 is a sensitive marker of inflammation that plays dual roles, pathogenic and cardioprotective, in the progression of cardiovascular diseases. Inflammation is intimately involved in salt‐induced hypertension. We investigated the responses of pentraxin‐3 to sodium and potassium supplementation to elucidate the potential role of pentraxin‐3 in salt‐induced hypertension. A total of 48 participants from northwest China were enrolled. All participants were maintained on a 3‐day normal diet, which was sequentially followed by a 7‐day low‐sodium diet, a 7‐day high‐sodium diet, and a 7‐day high‐sodium plus potassium diet. Plasma concentrations of pentraxin‐3 were assessed using ELISA. Plasma pentraxin‐3 decreased significantly during the low‐salt period compared to baseline (0.57 ± 0.19 ng/mL vs 0.72 ± 0.33 ng/mL, P = .012) and increased during the high‐salt period (0.68 ± 0.26 ng/mL vs 0.57 ± 0.19 ng/mL, P = .037). Potassium supplementation inhibited salt‐induced increase in pentraxin‐3 (0.56 ± 0.21 ng/mL vs 0.68 ± 0.26 ng/mL, P = .015). Ln‐transformed pentraxin‐3 at baseline was inversely correlated with BMI (r = −.349, P = .02), DBP (r = −.414, P = .005), MAP (r = −.360, P = .017). We found a positive correlation between the ln‐transformed concentrations of pentraxin‐3 and 24‐hour urinary sodium during low and high Na+ periods (r = .269, P = .012) and a negative relationship with 24 hours urinary potassium excretion during high‐salt and high‐salt plus potassium periods (r = −.246, P = .02). These correlations remained significant after adjusting for confounders. Pentraxin‐3 responses were more prominent in salt‐sensitive individuals than salt‐resistant individuals. Dietary salt and potassium interventions significantly altered circulating pentraxin‐3.
A panel consisting of three novel circulating lncRNAs, is it a predictive tool for gastric cancer?
Authors: Liu Jingjing , Wang Jiajun , Song Yongxi , Ma Bin , Luo Junlong , Ni Zhongran , Gao Peng , Sun Jingxu , Zhao Junhua , Chen Xiaowan , Wang Zhenning
Published: April 2018

Early detection is vital for prolonging 5‐year survival for patients with gastric cancer (GC). Numerous studies indicate that circulating long non‐coding RNAs (lncRNAs) can be used to diagnose malignant tumours. This study aimed to investigate the capacity of novel lncRNAs for diagnosing GC. A lncRNA microarray assay was used to screen differentially expressed lncRNAs between plasma of patients with GC and healthy controls. Plasma samples from 100 patients with healthy controls were used to construct a multiple‐gene panel. An additional 50 pairs of GC patients with healthy controls were used to evaluate the diagnostic accuracy of the panel. Expression levels of lncRNAs were quantified through real‐time polymerase chain reaction. The receiver operating characteristic curve and area under curve (AUC) were used to estimate the diagnostic capacity. We identified three lncRNAs, CTC‐501O10.1, AC100830.4 and RP11‐210K20.5 that were up‐regulated in the plasma of GC patients with AUCs 0.724, 0.730 and 0.737, respectively (P < .01). Based on the logistic regression model, the combined AUC of the three lncRNAs was 0.764. The AUC of the panel was 0.700 in the validation cohort. These findings indicate that plasma lncRNAs can serve as potential biomarkers for detection of GC.
Telocytes and interstitial cells of Cajal in the biliary system
Authors: Chen Lei , Yu Baoping
Published: April 2018

A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal‐like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles in physiological and pathophysiological processes.
Using learning flexibly and remembering after a delay: understanding cognitive dysfunction in adults with Down syndrome
Authors: Roberts L. , Richmond J. L.
Published: April 2018

Background

Episodic memory deficits are a characteristic of cognitive dysfunction in people with Down syndrome (DS). However, less is known about the processes (i.e. encoding, retention or using learned information flexibly) that underlie these deficits.

Method

We explored these abilities by administering a relational memory and inference task to participants with DS and mental age‐matched controls and testing both immediately and after a 24‐h delay.

Results

Adults with DS learned paired associates more slowly than controls but showed good recognition at both the immediate and delayed tests. Despite memory for learned pairs, adults with DS were less able to use relational learning flexibly to make inferential judgements than controls.

Conclusions

These results deepen our understanding of the cognitive profile of adults with DS, demonstrating deficits in both encoding new information, and flexibly using such information. These results have important implications for workplace training and intervention programs for people with DS.
An examination of perceptions of individuals with an intellectual disability, with and without co‐morbid schizophrenia: effects of labels on stigma
Authors: Rasdale A. R. , Warman D. M. , Phalen P. L.
Published: April 2018

Background

Research demonstrates negative perceptions of individuals with intellectual disabilities (ID) and individuals with schizophrenia, but no study has examined ID with a co‐morbid psychiatric disorder. The present study examined the social distance desired from and perceptions of dangerousness of ID, schizophrenia and co‐morbid schizophrenia and ID and examined the impact of providing a label for the behaviours presented in a vignette.

Methods

A total of 160 participants, all university students, were randomly assigned to one of six vignettes detailing a person with schizophrenia, ID, or a person with both presenting problems. Half of the participants were randomly assigned to read vignettes that had a label provided for the behaviours of the target.

Results

Participants desired more social distance from the unlabelled than labelled targets. Presence of schizophrenia resulted in increased social distance, but co‐morbid ID and schizophrenia elicited less desire for social distance than schizophrenia alone. Schizophrenia resulted in more perceived danger, but labelled co‐morbid schizophrenia and ID resulted in little perceived danger.

Conclusions

Labels resulted in positive outcomes, particularly, when ID was co‐morbid with schizophrenia. Schizophrenia stigma appears to be impacted by an ID label, indicating educating the public about the spectrum of co‐morbidity may be useful.
Spending Reversals and Fiscal Multipliers under an Interest Rate Peg
Authors: LI RONG , TIAN XIAOHUI
Published: April 2018

This paper examines whether fiscal stimuli are more effective when the monetary policy is less responsive to inflation. First, we provide empirical evidence suggesting that, in the period of U.S. passive monetary policy, a positive government spending shock was followed over time by a spending cut. Second, our theoretical analysis reveals that the pegged nominal interest rate is not a sufficient condition to generate a large fiscal multiplier. An increase in government spending could increase the long‐run real interest rate, if it is associated with a government spending reversal and a less responsive monetary policy. Consequently, the response of private consumption can be negative and the government spending multiplier is not necessarily greater than 1.
Ruga Lumina: Folding Interior Skin with Dynamic Light
Authors: Wu Jiangmei
Published: April 2018

Ruga Lumina investigates body–space relationships by leveraging digital fabrication and interactive technologies. Ruga Lumina is a spatial construct in the form of a smart luminous “skin” made of thin sheets of folded material that respond to the movement of live bodies within and surrounding its interior space. Spatial occupancy is registered through the use of smart technology; sensor information activates illumination and lighting effects, which, in turn, prompts perceptual and expressive aesthetic qualities as affects. This visual essay gives an account of the construction of Ruga Lumina at two exhibition sites: Detroit Center for Design and Technology (DCDT) in Detroit, Michigan, and 3Labs in Culver City, California. This account describes how bodies can be read and registered upon a spatial surface that points to a potential to re–envision fundamental notions of surface interiority.
Biological control potential of plant growth‐promoting rhizobacteria suppression of Meloidogyne incognita on cotton and Heterodera glycines on soybean: A review
Authors: Xiang Ni , Lawrence Kathy S. , Donald Patricia A.
Published: April 2018

Over the past decade, we have seen an increasing market for biopesticides and an increase in number of microbial control studies directed towards plant‐parasitic nematodes. This literature survey provides an overview of research on biological control of two economically important plant‐parasitic nematodes, Meloidogyne incognita (Kofoid & White) Chitwood (southern root‐knot nematode) and Heterodera glycines Ichinohe (soybean cyst nematode) using spore‐forming plant growth‐promoting rhizobacteria (PGPR). In this review, the current biological control strategies for the management of those cotton and soybean nematodes, the mechanism of using BacillusPGPR for biological control of plant‐parasitic nematode including induced systemic resistance and antagonism and the future of biological control agents on management of plant‐parasitic nematodes are covered.
Repeat retropubic suburethral sling procedure is effective for recurrent female stress urinary incontinence
Authors: Ong Hueih Ling , Jiang Yuan‐Hong , Kuo Hann‐Chorng
Published: April 2018

Objective

The aim of the present study was to investigate the effectiveness of repeat retropubic suburethral sling for recurrent stress urinary incontinence (SUI) in women.

Methods

A retrospective review was performed of 35 women with SUI who underwent repeat retropubic suburethral sling procedures between May 1994 and November 2014. Treatment outcome was assessed directly or by telephone interview. Sling position and urethral incompetence during straining and coughing after the procedure were evaluated.

Results

The overall continence rate after repeat suburethral sling procedures was 60% (21/35). Among the 35 women, 19 underwent a simple retropubic suburethra sling procedure and 16 underwent combined suburethral sling and other pelvic floor surgery; the success rate for these 2 groups was 84.2% (16/19) and 31.3% (5/16; P = .001), respectively. The success rate was 60% in patients with normal detrusor function (n = 18/30) and in those with detrusor underactivity (n = 3/5; P = 1.0). For patients with intrinsic sphincter deficiency and bladder base hypermobility, the success rate was 63.6% (n = 14/22) and 53.8% (n = 7/13), respectively (P = .36). Among the 25 patients with transrectal ultrasound follow‐up data, the success rate following placement of the second sling at the bladder neck, proximal urethra, middle urethra, and distal urethra was 50% (2/4), 87.5% (7/8), 36.4% (4/11), and 0% (0/2), respectively (P = .122).

Conclusion

Repeat suburethral sling procedures for recurrent SUI are safe and effective. The position of the second sling at the proximal urethra resulted in a relatively higher continence rate relative to other sites.
Fluorescent labeling of endogenous platelets for intravital microscopy: Effects on platelet function
Authors: Da Qi , Derry Paul J. , Lam Fong W. , Rumbaut Rolando E.
Published: April 2018

Objective

Monitoring endogenous platelets during intravital microscopy often involves two approaches: fluorescently labeled antibodies or genetic models of platelet‐specific fluorescent protein expression. Due to limited data available on platelet functional changes induced by these methods, we compared functional effects of these methods on platelets.

Methods

Platelet aggregation to collagen and thrombin, and collagen matrix‐mediated platelet adhesion/aggregation under flow were tested. We assessed platelets from mice expressing EYFP on platelets (Cre(+)), littermate controls (Cre(−)), C57BL/6 mice, and platelets from vehicle control and x‐488 treatment. We utilized intravital microscopy to monitor platelets in vivo using Cre(+) mice and x‐488 treatment.

Results

Both genetic and antibody‐based approaches yielded substantial platelet‐specific fluorescence. Platelets from Cre(+) and Cre(−) mice behaved similarly in aggregation and adhesion/aggregation under flow. However, they exhibited significantly enhanced aggregation and higher adhesion/aggregation as compared to platelets from C57BL/6 mice. Compared to vehicle control, x‐488 platelet labeling did not induce significant functional changes in vitro. Both methods of platelet labeling provided satisfactory platelet detectability in vivo.

Conclusions

x‐488 antibody labeling of platelets induced less alteration of platelet function than genetic approaches under our experimental conditions and seems more suitable for monitoring of endogenous platelets.
Nature of nursing errors and their contributing factors in intensive care units
Authors: Eltaybani Sameh , Mohamed Nadia , Abdelwareth Mona
Published: April 2018

Background

Errors tend to be multifactorial and so learning from nurses' experiences with them would be a powerful tool toward promoting patient safety.

Aim

To identify the nature of nursing errors and their contributing factors in intensive care units (ICUs).

Methods

A semi‐structured interview with 112 critical care nurses to elicit the reports about their encountered errors followed by a content analysis.

Results

A total of 300 errors were reported. Most of them (94·3%) were classified in more than one error category, e.g. ‘lack of intervention’, ‘lack of attentiveness’ and ‘documentation errors’: these were the most frequently involved error categories. Approximately 40% of reported errors contributed to significant harm or death of the involved patients, with system‐related factors being involved in 84·3% of them. More errors occur during the evening shift than the night and morning shifts (42·7% versus 28·7% and 16·7%, respectively). There is a statistically significant relation (p ≤ 0·001) between error disclosure to a nursing supervisor and its impact on the patient.

Conclusions

Nurses are more likely to report their errors when they feel safe and when the reporting system is not burdensome, although an internationally standardized language to define and analyse nursing errors is needed. Improving the health care system, particularly the managerial and environmental aspects, might reduce nursing errors in ICUs in terms of their incidence and seriousness.

Relevance to clinical practice

Targeting error‐liable times in the ICU, such as mid‐evening and mid‐night shifts, along with improved supervision and adequate staff reallocation, might tackle the incidence and seriousness of nursing errors. Development of individualized nursing interventions for patients with low health literacy and patients in isolation might create more meaningful dialogue for ICU health care safety.
Molecular data to elucidate the taxonomy of Seseli sect. Seseli (Apiaceae) in east Mediterranean and southern Europe
Authors: Lyskov Dmitry , Güner Ebru Doğan , Samigullin Tahir , Duman Hayri , Pimenov Michael
Published: April 2018

The taxonomy of the type section of the genus Seseli is revised based on newly obtained molecular data. The type species of the genus, Seseli tortuosum, is shown to be a polyphyletic taxon and is split into two species: the western Mediterranean S. tortuosum and the eastern Mediterranean S. arenarium. The Turkish endemics S. hartvigii, S. serpentinum and S. andronakii, and the Transcaucasian S. grandivittatum form a complex of closely related species together with S. arenarium. The results of the molecular analysis confirm the specific rank of S. corymbosum, S. phrygium and S. paphlagonicum and the status of S. gummiferum as distinct from either of these three. The latter species is strictly endemic to Crimea and does not occur in Turkey.
When all seems lost: management of refractory constipation—Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more
Authors: Wilkinson‐Smith V. , Bharucha A. E. , Emmanuel A. , Knowles C. , Yiannakou Y. , Corsetti M.
Published: April 2018

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited.
Quantifying Rome symptoms for diagnosis of the irritable bowel syndrome
Authors: Chang J. Y. , Almazar A. E. , Richard Locke G. , Larson J. J. , Atkinson E. J. , Talley N. J. , Saito Y. A.
Published: April 2018

Background

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, diagnosed on symptom‐based criteria. Many have reported discrepancies between formal Rome criteria and diagnoses made in clinical practice. The aim of the study was to explore whether a quantitative version of the Rome criteria would better represent a clinical diagnosis of IBS than the current dichotomous criteria for symptom measure.

Methods

As part of a large, case‐control study, participants completed a validated bowel disease questionnaire. Rome criteria were analyzed based on 15 individual symptoms. Penalized logistic regression model with stepwise selection was used to identify significant symptoms of IBS which were independently associated with case‐control status.

Key Results

In cases with a clinical diagnosis of IBS, 347 (70%) met Rome criteria for IBS. Increasing number of Rome symptoms were found related to the odds of being diagnosed with IBS. Nearly half of the Rome‐negative case group experienced infrequent symptoms suggesting milder disease. Five of 15 Rome symptoms were associated with predicting case‐control status in the final model, with 96% correctly classified among Rome‐positive cases, 76% for Rome‐negative cases, and 91% for controls.

Conclusions and Inferences

Irritable bowel syndrome appears to be a spectrum disorder. Quantifying individual symptoms of Rome criteria has greater utility than the current application in representing the degree of IBS affectedness and appears to better reflect a clinical diagnosis of IBS applied by physicians. The use of a quantitative diagnostic Rome “score” may be helpful in clinical practice and research studies to better reflect the degree an individual is affected with IBS.
Reduction in pain: Is it worth the gain? The effect of opioids on the GI tract
Authors: Nee J. , Rangan V. , Lembo A.
Published: April 2018

The use of opioid medications for acute and chronic pain has increased significantly in the past 20 years in the United States. Given the high density of opioid receptors in the gastrointestinal tract, side effects are common in these patients including constipation, dysphagia, bloating, nausea, and vomiting. These side effects, which are experienced by most patients who take opioids, can lead to significant impairment in quality of life. Unlike other side effects from opioids, gastrointestinal side effects do not diminish with continued use, often leading patients to reduce or discontinue their opioid treatment to relieve these side effects. Therefore, physicians must be aware and anticipate potential side effects in patients receiving opioids to ensure appropriate pain management.
The tomato Ethylene Response Factor Sl‐ERF.B3 integrates ethylene and auxin signaling via direct regulation of Sl‐Aux/IAA27
Authors: Liu Mingchun , Chen Yao , Chen Ya , Shin Jun‐Hye , Mila Isabelle , Audran Corinne , Zouine Mohamed , Pirrello Julien , Bouzayen Mondher
Published: April 2018

Plant growth and development is coordinated by complex networks of interacting hormones, and cross‐talk between ethylene and auxin signaling is essential for a wide range of plant developmental processes. Nevertheless, the molecular links underlying the interaction between the two hormones remain poorly understood.

In order to decipher the cross‐talk between the Ethylene Response Factor Sl‐ERF.B3 and Sl‐IAA27, mediating ethylene and auxin signaling, respectively, we combined reverse genetic approaches, physiological methods, transactivation experiments and electrophoretic mobility shift assays.

Sl‐ERF.B3 is responsive to both ethylene and auxin and ectopic expression of its dominant repressor version (ERF.B3‐SRDX) results in impaired sensitivity to auxin with phenotypes recalling those previously reported for Sl‐IAA27 downregulated tomato lines. The expression of Sl‐IAA27 is dramatically reduced in the ERF.B3‐SRDX lines and Sl‐ERF.B3 is shown to regulate the expression of Sl‐IAA27 via direct binding to its promoter.

The data support a model in which the ethylene‐responsive Sl‐ERF.B3 integrates ethylene and auxin signaling via regulation of the expression of the auxin signaling component Sl‐IAA27. The study uncovers a molecular mechanism that links ethylene and auxin signaling in tomato.
Arabidopsis pollen tube germination and growth depend on the mitochondrial calcium uniporter complex
Authors: Selles Benjamin , Michaud Caroline , Xiong Tou‐cheu , Leblanc Olivier , Ingouff Mathieu
Published: April 2018

The mitochondrial calcium uniporter complex (MCUc) was recently characterized in details in metazoans and consists of pore‐forming units (MCUs) and regulatory factors that channel calcium (Ca2+) ion into the mitochondria. MCUs participate in many stress and developmentally related processes involving Ca2+.

Although multiple homologues of MCUs and one regulatory subunit are usually present in plants, the first functional characterization and contribution to Ca2+ related processes of these proteins have been reported recently. Here, we focused on two predicted Arabidopsis MCUs and studied their role in the germination and the growth of pollen tube, a tip‐growing cell type highly dependent on Ca2+ homeostasis.

Heterologous expression of MCU1 or MCU2 in yeast is sufficient to generate a mitochondrial Ca2+ influx. MCU1 and MCU2 fluorescent reporters are co‐expressed in the vegetative cell mitochondria of the pollen grain but are undetectable in the embryo sac. We demonstrate that MCU1 and MCU2 can form a heterotypic complex. Phenotypic analyses revealed an impaired pollen tube germination and growth in vitro only for the mcu2 mutants suggesting a predominant role of MCU2.

Our results show that mitochondrial Ca2+ controlled by MCUs is an additional player in Arabidopsis pollen tube germination and growth.
Inter‐individual differences in weight change following exercise interventions: a systematic review and meta‐analysis of randomized controlled trials
Authors: Williamson P. J. , Atkinson G. , Batterham A. M.
Published: April 2018

Previous reports of substantial inter‐individual differences in weight change following an exercise intervention are often based solely on the observed responses in the intervention group. Therefore, we aimed to quantify the magnitude of inter‐individual differences in exercise‐mediated weight change. We synthesized randomized controlled trials (RCTs) of structured, supervised exercise interventions. Fourteen electronic databases were searched for relevant studies published up to March 2017. Search terms focused on structured training, RCTs and body weight. We then sifted these results for those RCTs (n = 12, 1500 participants) that included relevant comparator group data. Standard deviations (SDs) of weight change were extracted, thereby allowing the SD for true inter‐individual differences in weight loss to be calculated for each study. Using a random effects meta‐analysis, the pooled SD (95% CI) for true individual responses was 0.8 (−0.9 to 1.4) kg. The 95% prediction interval (based on 2SDs) for true inter‐individual responses was −2.8 to 3.6 kg. The probability (% chance) that the true individual response variability would be clinically meaningful (>2.5 kg) in a future study in similar settings was 23% (‘unlikely’). Therefore, we conclude that evidence is limited for the notion that there are clinically important individual differences in exercise‐mediated weight change.
Chronic mucocutaneous candidiasis due to gain‐of‐function mutation in STAT1
Authors: Carey Barbara , Lambourne Jonathan , Porter Stephen , Hodgson Tim
Published: April 2018

Chronic mucocutaneous candidiasis (CMC) is a heterogenous group of primary immunodeficiency diseases characterised by susceptibility to chronic or recurrent superficial Candida infection of skin, nails and mucous membranes. Gain‐of‐function mutations in the STAT1 gene (STAT1‐GOF) are the most common genetic aetiology for CMC, and mutation analysis should be considered. These mutations lead to defective responses in Type 1 and Type 17 helper T cells (Th1 and Th17), which, depending on the mutation, also predispose to infection with Staphylococci, Mycobacteria and Herpesviridae. We describe the clinical and genetic findings for three patients with CMC due to gain‐of‐function mutations in the STAT1 gene.
Between cheap talk and epistocracy: The logic of interest group access in the European Parliament's committee hearings
Authors: Coen David , Katsaitis Alexander
Published: April 2018

Improving policy deliberation is a central objective for the European Union's institutions. Focusing on the European Parliament's committee hearings as an understudied area of European governance, we aim to understand their role, and their capacity to improve its procedural legitimacy. Building on theoretical work on interest group access and deliberation we argue that hearings can serve three purposes: (i) coordinative; (ii) epistemic; (iii) enhancing public participation. We construct a set of measures and assess an entire population of participants in hearings (2009–14), concentrating on three committees. Our analyses show that hearings serve a hybrid purpose between coordinative and epistemic. At the top end, we observe a core group of gatekeepers representing the dominant constituencies. Simultaneously, research organizations are granted unique access as experts that de‐politicize debates. Theoretically, we contribute to discussions on interest group access while providing an innovative set of tools for its measurement, and the first dataset of its kind.
Prevention of perioperative venous thromboembolism in pediatric patients: Guidelines from the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI)
Authors: Morgan Judith , Checketts Matthew , Arana Amaia , Chalmers Elizabeth , Maclean Jamie , Powis Mark , Morton Neil ,   the Association of Paediatric Anaesthetists of Great Britain and Ireland Guidelines Working Group on Thromboprophylaxis in Children
Published: April 2018

The Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) Guidelines Working Group on Thromboprophylaxis in Children has reviewed the literature and where possible provided advice on the care of children in the perioperative period. Areas reviewed include the incidence of perioperative venous thromboembolism (VTE), risk factors, evidence for mechanical and chemical prophylaxis, and complications. Safe practice of regional anesthesia with anticoagulant prophylaxis is detailed. In summary, there are few areas of strong evidence. Routine prophylaxis cannot be recommended for young children. Postpubertal adolescents (approximately 13 years and over) are at a slightly increased risk of VTE and should be assessed for prophylaxis and may warrant intervention if other risk factors are present. However, the incidence of VTE is significantly lower than in the adult population. This special interest review presents a summary and discussion of the key recommendations, a decision‐making algorithm and a risk assessment chart. For the full guideline, go to www.apagbi.org.uk/publications/apa-guidelines.
Consensus statement on clear fluids fasting for elective pediatric general anesthesia
Authors: Thomas Mark , Morrison Christa , Newton Richard , Schindler Ehrenfried
Published: April 2018

Pediatric anesthetic guidelines for the management of preoperative fasting of clear fluids are currently 2 hours. The traditional 2 hours clear fluid fasting time was recommended to decrease the risk of pulmonary aspiration and is not in keeping with current literature. It appears that a liberalized clear fluid fasting regime does not affect the incidence of pulmonary aspiration and in those who do aspirate, the sequelae are not usually severe or long‐lasting. With a 2‐hour clear fasting policy, the literature suggests that this translates into 6‐7 hours actual duration of fasting with several studies up to 15 hours. Fasting for prolonged periods increases thirst and irritability and results in detrimental physiological and metabolic effects. With a 1‐hour clear fluid policy, there is no increased risk of pulmonary aspiration and studies demonstrate the stomach is empty. There is less nausea and vomiting, thirst, hunger, and anxiety, if allowed a drink closer to surgery. Children appear more comfortable, better behaved and possibly more compliant. In children less than 36 months this has positive physiological and metabolic effects. It is practical to allow children to drink until 1 hour prior to anesthesia on the day of surgery. In this joint consensus statement, the Association of Paediatric Anaesthetists of Great Britain and Ireland, the European Society for Paediatric Anaesthesiology, and L'Association Des Anesthésistes‐Réanimateurs Pédiatriques d'Expression Française agree that, based on the current convincing evidence base, unless there is a clear contraindication, it is safe and recommended for all children able to take clear fluids, to be allowed and encouraged to have them up to 1 hour before elective general anesthesia.
The impact of general anesthesia on child development and school performance: a population‐based study
Authors: Schneuer Francisco J , Bentley Jason P , Davidson Andrew J , Holland Andrew JA , Badawi Nadia , Martin Andrew J , Skowno Justin , Lain Samantha J , Nassar Natasha
Published: April 2018

Background

There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood.

Aims

The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood.

Methods

We included children born in New South Wales, Australia of 37+ weeks’ gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade‐3 school test results in 2008‐2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests.

Results

Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.07‐1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21‐1.48) and reading (aOR: 1.23; 95% CI: 1.12‐1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained.

Conclusion

Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations.
Reverse modelling to estimate yield losses caused by crop diseases
Authors: Willocquet L. , Félix I. , de Vallavieille‐Pope C. , Savary S.
Published: April 2018

Yield loss analysis is critical to inform tactical and strategic decisions in crop health management, and requires quantification of three elements: the levels of injury caused by disease or pest, the actual (injured) yield, and the attainable (uninjured) yield. Reverse modelling allows reconstruction of an object or a process from limited information combined with a mathematical model. This approach is applied to estimate yield losses caused by diseases in winter wheat using a process‐based simulation model (WHEATPEST), in combination with field data generated by a network of experiments across France, where multiple disease injuries and actual yields, but not attainable yields, were measured. The analysis covers 70 [year × region × variety × crop management] combinations encompassing five years (2004–2008), four French regions, two winter wheat varieties (one high‐yielding and one hardy variety), and two levels of crop management corresponding to two levels of chemical intensification. The analysis involved three main successive modelling steps where actual yield, attainable yield and yield losses associated with individual diseases were simulated. Overall, simulated yield losses to combined diseases ranged from 0 to 4.2 t ha−1, and averaged 0.80 t ha−1. Septoria tritici blotch caused the highest mean yield loss of 0.66 t ha−1. The results highlight the contribution of varietal improvement to agricultural sustainability and performances. Reverse modelling can be applied to other crops and diseases or pests, in order to estimate individual and combined disease yield losses.
M/XDR‐TB treatment perspective: How to avoid mountains of pills via digital technologies – Reply
Authors: Dheda Keertan ,   on behalf of all authors
Published: April 2018

See Letter
The microeconomic impact of political instability: Firm‐level evidence from Tunisia
Authors: Matta Samer , Appleton Simon , Bleaney Michael
Published: April 2018

This paper explores the impact of political instability on firms in the context of Tunisia, which experienced a surge in political instability events after the 2011 Jasmine revolution. Using a new dataset, we show that political instability was a major concern for small and exporting firms as well as those that were operating in the tourism sector, those that suffered from acts of vandalism or arson, and those that were located in the interior region of Tunisia. More importantly, we find strong evidence that political instability was the most damaging constraint to firm growth in Tunisia after the Arab Spring.
Multivariate Latent Variable Transition Models of Longitudinal Mixed Data: An Analysis on Alcohol Use Disorder
Authors: Cagnone Silvia , Viroli Cinzia
Published: April 2018

Alcohol abuse is a dangerous habit in young people. The National Youth Survey is a longitudinal American study in part devoted to the investigation of alcohol disorder over time. The symptoms of alcohol disorder are measured by binary and ordinal items. In the literature it is well recognized that alcohol abuse can be measured by a latent construct; therefore generalized latent variable models for mixed data represent the ideal framework to analyse these data. However, it might be desirable to cluster individuals according to the different severity of their alcohol use disorder and to investigate how the groups vary over time. We present a new methodological framework that includes two levels of latent variables: one continuous hidden variable for dimension reduction and clustering and a discrete random variable accounting for the dynamics of alcohol disorder symptoms. The effect of covariates is also measured and a testing procedure for the temporal assumption is developed. This work addresses three important issues. First, it represents a unified framework for the analysis of longitudinal multivariate mixed data. Secondly, it captures and models the unobserved heterogeneity of the data. Finally it describes the dynamics of the data through the definition of latent constructs.