The information sources and journals consulted or read by UK paediatricians to inform their clinical practice and those which they consider important: a questionnaire survey

Background: Implementation of health research findings is important for medicine to be evidence-based. Previous studies have found variation in the information sources thought to be of greatest importance to clinicians but publication in peer-reviewed journals is the traditional route for dissemination of research findings. There is debate about whether the impact made on clinicians should be considered as part of the evaluation of research outputs. We aimed to determine first which information sources are generally most consulted by paediatricians to inform their clinical practice, and which sources they considered most important, and second, how many and which peer-reviewed journals they read. Methods: We enquired, by questionnaire survey, about the information sources and academic journals that UK medical paediatric specialists generally consulted, attended or read and considered important to their clinical practice. Results: The same three information sources – professional meetings & conferences, peerreviewed journals and medical colleagues – were, overall, the most consulted or attended and ranked the most important. No one information source was found to be of greatest importance to all groups of paediatricians. Journals were widely read by all groups, but the proportion ranking them first in importance as an information source ranged from 10% to 46%. The number of journals read varied between the groups, but Archives of Disease in Childhood and BMJ were the most read journals in all groups. Six out of the seven journals previously identified as containing best paediatric evidence are the most widely read overall by UK paediatricians, however, only the two most prominent are widely read by those based in the community. Conclusion: No one information source is dominant, therefore a variety of approaches to Continuing Professional Development and the dissemination of research findings to paediatricians should be used. Journals are an important information source. A small number of key ones can be identified and such analysis could provide valuable additional input into the evaluation of clinical research outputs

Relationship among research collaboration, number of documents and number of citations. A case study in Spanish computer science production in 2000-2009.

This paper analyzes the relationship among research collaboration, number of documents and number of citations of computer science research activity. It analyzes the number of documents and citations and how they vary by number of authors. They are also analyzed (according to author set cardinality) under different circumstances, that is, when documents are written in different types of collaboration, when documents are published in different document types, when documents are published in different computer science subdisciplines, and, finally, when documents are published by journals with different impact factor quartiles. To investigate the above relationships, this paper analyzes the publications listed in the Web of Science and produced by active Spanish university professors between 2000 and 2009, working in the computer science field. Analyzing all documents, we show that the highest percentage of documents are published by three authors, whereas single-authored documents account for the lowest percentage. By number of citations, there is no positive association between the author cardinality and citation impact. Statistical tests show that documents written by two authors receive more citations per document and year than documents published by more authors. In contrast, results do not show statistically significant differences between documents published by two authors and one author. The research findings suggest that international collaboration results on average in publications with higher citation rates than national and institutional collaborations. We also find differences regarding citation rates between journals and conferences, across different computer science subdisciplines and journal quartiles as expected. Finally, our impression is that the collaborative level (number of authors per document) will increase in the coming years, and documents published by three or four authors will be the trend in computer science literature

The NR4A subgroup: immediate early response genes with pleiotropic physiological roles

The nuclear hormone receptor (NR) superfamily includes the orphan NR4A subgroup, comprised of Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3). These NRs are classified as early response genes, are induced by a diverse range of signals, including fatty acids, stress, growth factors, cytokines, peptide hormones, phorbol esters, neurotransmitters, and physical stimuli (for example magnetic fields, shear stress). The ability to sense and rapidly respond to changes in the cellular environment thus appears to be a hallmark of this subfamily. The members of the NR4A subgroup are well conserved in the DNA binding domain (~91-95%) and the C-terminal ligand-binding domain (~60%), but are divergent in the N-terminal AB region. These receptors bind as monomers, homodimers and heterodimers with RXRs (to mediate retinoid signaling) to different permutations of the canonical NR binding motif. The NR4A subgroup activates gene expression in a constitutive ligand-independent manner. NR4A-mediated trans-activation (LBD) involves unusually active N-terminal AF-1 domains that mediate coactivator recruitment. Moreover, the NR4A receptors encode atypical LBDs and AF-2 domains. For example, the LBDs contain no cavity due to bulky hydrophobic residue side chains, and lack the classical coactivator-binding cleft constituted by helices 3, 4 and 12. However, a hydrophobic patch exists between helices 11 and 12, that encodes a novel cofactor interface that modulates transcriptional activity. In line with the pleiotropic physiological stimuli that induce the NR4A subgroup, these orphan NRs have been implicated in cell cycle regulation (and apoptosis), neurological disease, steroidogenesis, inflammation, carcinogenesis and atherogenesis

Cigarette smoke exposure facilitates allergic sensitization in mice

BACKGROUND: Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained. OBJECTIVE: The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4(+ )T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena. CONCLUSION: In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

The outcomes of midline versus medio-lateral episiotomy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Interaction of atopy and smoking on respiratory effects of occupational dust exposure: a general population-based study

BACKGROUND: For individual exposures, effect modification by atopy or smoking has been reported on the occurrence of occupational airway disease. It is unclear if effect modification can be studied in a general population by an aggregated exposure measure. Assess relationship between airway obstruction and occupational exposure using a job-exposure-matrix (JEM) classifying jobs into 3 broad types of exposure, and test for effect modification by atopy, and smoking. METHODS: Data from 1,906 subjects were analyzed, all participants of the European Community Respiratory Health Survey. Job titles were categorized by an a priori constructed job exposure matrix into three classes of exposure to respectively organic dust, mineral dust, and gases/ fumes. Relationships were assessed for 'current wheeze', bronchial hyperresponsiveness (BHR), 'current asthma' (wheeze+BHR), and 'chronic bronchitis' (morning phlegm or morning cough), and lung function. RESULTS: Subjects with organic dust exposure in their work environment more frequently had 'current asthma' (OR 1.48, 95% C.I. 0.95;2.30), and a lower FEV(1 )(-59 mL, 95% C.I. -114;-4). The relationship was only present in asthmatic workers, and their risk was four-fold greater than in subjects with either atopy or exposure alone. Mineral dust exposure was associated with 'chronic bronchitis' (OR 2.22, 95% C.I. 1.16;4.23) and a lower FEV(1)/FVC ratio (-1.1%, 95% C.I. -1.8;-0.3). We observed an excess risk in smokers, greater than the separate effects of smoking or mineral dust exposure together. CONCLUSION: Occupational exposure to organic dust is associated with an increased risk of asthma, particularly in atopics. Chronic bronchitis occurs more frequently among individuals exposed to mineral dust, and smoking doubles this risk

Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells' differentiation in vitro and in neurochemical models of Parkinson's disease

Antisense (AS) transcripts are RNA molecules that are transcribed from the opposite strand to sense (S) genes forming S/AS pairs. The most prominent configuration is when a lncRNA is antisense to a protein coding gene. Increasing evidences prove that antisense transcription may control sense gene expression acting at distinct regulatory levels. However, its contribution to brain function and neurodegenerative diseases remains unclear. We have recently identified AS Uchl1 as an antisense to the mouse Ubiquitin carboxy-terminal hydrolase L1 (Uchl1) gene (AS Uchl1), the synthenic locus of UCHL1/PARK5. This is mutated in rare cases of early-onset familial Parkinson's Disease (PD) and loss of UCHL1 activity has been reported in many neurodegenerative diseases. Importantly, manipulation of UchL1 expression has been proposed as tool for therapeutic intervention. AS Uchl1 induces UchL1 expression by increasing its translation. It is the representative member of SINEUPs (SINEB2 sequence to UP-regulate translation), a new functional class of natural antisense lncRNAs that activate translation of their sense genes. Here we take advantage of FANTOM5 dataset to identify the transcription start sites associated to S/AS pair at Uchl1 locus. We show that AS Uchl1 expression is under the regulation of Nurr1, a major transcription factor involved in dopaminergic cells' differentiation and maintenance. Furthermore, AS Uch1 RNA levels are strongly down-regulated in neurochemical models of PD in vitro and in vivo. This work positions AS Uchl1 RNA as a component of Nurr1-dependent gene network and target of cellular stress extending our understanding on the role of antisense transcription in the brain

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning