Failure of hospital employees to comply with smoke-free policy is associated with nicotine dependence and motives for smoking: A descriptive cross-sectional study at a teaching hospital in the United Kingdom

Abstract Background Smoke-free policy aims to protect the health of the population by reducing exposure to environmental tobacco smoke (ETS), and World Health Organisation (WHO) guidance notes that these policies are only successful if there is full and proper enforcement. We aimed to investigate the problem of resistance to smoking restrictions and specifically compliance with smoke-free policy. We hypothesised that an explanation for non-compliance would lie in a measurable difference between the smoking behaviours of compliant and non-compliant smokers, specifically that non-compliance would be associated with nicotine dependence and different reasons for smoking. Methods We conducted a questionnaire-based, descriptive, cross-sectional study of hospital employees. Seven hundred and four members of staff at Addenbrooke's Hospital, Cambridge, UK, completed the questionnaire, of whom 101 were smokers. Comparison between compliant and non-compliant smokers was made based on calculated scores for the Fagerström test and the Horn-Waingrow scale, and level of agreement with questions about attitudes. For ordinal data we used a linear-by-linear association test. For non-parametric independent variables we used the Mann-Whitney test and for associations between categorical variables we used the chi-squared test. Results The demographic composition of respondents corresponded with the hospital's working population in gender, age, job profile and ethnicity. Sixty nine smokers reported they were compliant while 32 were non-compliant. Linear-by-linear association analysis of the compliant and non-compliant smokers' answers for the Fagerström test suggests association between compliance and nicotine dependence (p = 0.049). Mann-Whitney test analysis suggests there is a statistically significant difference between the reasons for smoking of the two groups: specifically that non-compliant smokers showed habitual smoking behaviour (p = 0.003). Overall, compliant and non-compliant smokers did not have significantly different attitudes towards the policy or their own health. Conclusion We demonstrate that those who smoke in this setting in contravention to a smoke-free policy do so neither for pleasure (promotion of positive affect) nor to avoid feeling low (reduction of negative affect); instead it is a resistant habit, which has little or no influence on the smoker's mood, and is determined in part by chemical dependence

Conformational transition of FGFR kinase activation revealed by site-­specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

Confidentiality and public protection: ethical dilemmas in qualitative research with adult male sex offenders

This paper considers the ethical tensions present when engaging in in-depth interviews with convicted sex offenders. Many of the issues described below are similar to those found in other sensitive areas of research. However, confidentiality and public protection are matters that require detailed consideration when the desire to know more about men who have committed serious and harmful offences is set against the possibility of a researcher not disclosing previously unknown sensitive information that relates to the risk of someone being harmed.</p

Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo

Genetic Incorporation of Unnatural Amino Acids into Proteins in Mycobacterium tuberculosis

New tools are needed to study the intracellular pathogen Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), to facilitate new drug discovery and vaccine development. We have developed methodology to genetically incorporate unnatural amino acids into proteins in Mycobacterium smegmatis, BCG and Mtb, grown both extracellularly in culture and inside host cells. Orthogonal mutant tRNATyr/tyrosyl-tRNA synthetase pairs derived from Methanococcus jannaschii and evolved in Escherichia coli incorporate a variety of unnatural amino acids (including photocrosslinking, chemically reactive, heavy atom containing, and immunogenic amino acids) into proteins in response to the amber nonsense codon. By taking advantage of the fidelity and suppression efficiency of the MjtRNA/pIpaRS pair in mycobacteria, we are also able to use p-iodophenylalanine to induce the expression of proteins in mycobacteria both extracellularly in culture and inside of mammalian host cells. This provides a new approach to regulate the expression of reporter genes or mycobacteria endogenous genes of interest. The establishment of the unnatural amino acid expression system in Mtb, an intracellular pathogen, should facilitate studies of TB biology and vaccine development

Social deprivation and exposure to health promotion. A study of the distribution of health promotion resources to schools in England

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 Chivu and ReidpathBACKGROUND: Area deprivation is a known determinant of health. It is also known that area deprivation is associated with lower impact health promotion. It is less well known, however, whether deprived areas are less responsive to health promotion, or whether they are less exposed. Using data from a national, school-based campaign to promote vaccination against the human papilloma virus (HPV), the relationship between area deprivation and exposure was examined. METHODS: Taking advantage of a health promotion campaign to provide information to schools about HPV vaccination, a cross sectional study was conducted to examine the relationship between area level, social deprivation, and take-up of (i.e., exposure to) available health promotion material. The sample was 4,750 schools across England, including government maintained and independent schools. The relationship between area deprivation and exposure was examined using bi- and multivariate logistic regression. RESULTS: It was found that schools in the least deprived quintile had 1.32 times the odds of requesting health promotion materials than schools in the most deprived areas (p = .01). This effect was independent of the school size, the type of school, and the geographic region. Conclusion The relationship between area deprivation and the impact of health promotion may be due, at least in part, to differential levels of exposure. The study was limited in scope, pointing to the need for more research, but also points to potentially important policy implications

Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane

Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane

Long-term myocardial recovery after mitral valve replacement in noncompaction cardiomyopathy

Isolated noncompaction of the left ventricle is a congenital cardiomyopathy, which has been described recently, with literature limited to case reports and case series. Even though various complications have been reported with noncompaction cardiomyopathy, among them severe mitral regurgitation has been reported recently in a few cases. There is no great evidence in the literature about its management, apart from some cases of mitral valve repair and replacement in young patients. We are reporting a case of an elderly lady with isolated left ventricular noncompaction cardiomyopathy associated with severe mitral regurgitation treated with mitral valve replacement with one and half year of follow up demonstrating significant myocardial recovery

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p