Harmless? A hierarchical analysis of poppers use correlates among young gay and bisexual men

© 2019 Australasian Professional Society on Alcohol and other Drugs Introduction and Aims: Poppers (alkyl nitrites) are recreational substances commonly used during sexual activity. The current legal status of poppers is complex and wide-ranging bans are increasingly under discussion. Research has identified disproportionate levels of poppers use in sexual minority men. While research on poppers use among sexual minority men exists, little is known about poppers use patterns and correlations with psychosocial and other factors among gay and bisexual young men. Design and Methods: A cross-sectional survey was conducted with 836 Australian gay and bisexual young men aged 18 to 35 years. Descriptive statistics and hierarchical segmentation analyses were conducted to identify poppers use patterns, and correlates of recent poppers use (past 3 months) with personal characteristics, use of other substances, as well as mental and psychosocial health including minority stress, LGBT-community connectedness and participation. Results: High levels of lifetime (38%, n = 315) and recent (24%, n = 204) poppers use were reported. However, few participants reported dependency symptoms, risky consumption or problems arising from using poppers. The final model included three variables (visiting sex-on-premises venues, licensed LGBT venues, and using other substances) and predicted 85% (n = 174) of recent poppers use. No correlations with other concepts or characteristics could be identified. Conclusion: This analysis further supports the hypothesis that poppers may be substances with a comparably low-risk profile. A regulation of poppers with a harm reduction approach may present a valuable public health intervention

A study of the distribution of phylogenetically conserved blocks within clusters of mammalian homeobox genes

Genome sequencing efforts of the last decade have produced a large amount of data, which has enabled whole-genome comparative analyses in order to locate potentially functional elements and study the overall patterns of phylogenetic conservation. In this paper we present a statistically based method for the characterization of these patterns in mammalian DNA sequences. We have applied this approach to the study of exceptionally well conserved homeobox gene clusters (Hox), based on an alignment of six species, and we have constructed a map of Hox cataloguing the conserved fragments, along with their locations in relation to the genes and other landmarks, sometimes showing unexpected layouts

A ChIP-Seq Benchmark Shows That Sequence Conservation Mainly Improves Detection of Strong Transcription Factor Binding Sites

Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS) is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial.Here we use published ChIP-seq data and an improved peak detection method to create comprehensive benchmark datasets for prediction methods which use known descriptors or binding motifs to detect TFBS in genomic sequences. We use this benchmark to assess the performance of five different prediction methods and find that the methods that use information about sequence conservation generally perform better than simpler motif-scanning methods. The difference is greater on high-affinity peaks and when using short and information-poor motifs. However, if the motifs are specific and information-rich, we find that simple motif-scanning methods can perform better than conservation-based methods.Our benchmark provides a comprehensive test that can be used to rank the relative performance of transcription factor binding site prediction methods. Moreover, our results show that, contrary to previous reports, sequence conservation is better suited for predicting strong than weak transcription factor binding sites

Azacytidine and Decitabine Induce Gene-Specific and Non-Random DNA Demethylation in Human Cancer Cell Lines

The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1) and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation

Linking the sectoral employment structure and household poverty in the United Kingdom

Structural changes in the labour markets of developed economies, and changes in their institutional characteristics, have led to growing unease about the nature of low-paid employment. Related concerns have been expressed about the persistence of low-pay, the fragmentation of work and the growth of under-employment. While all these factors have potential implications for individuals’ earnings, less is known about the connection between labour market change, patterns of sectoral growth and decline and household poverty outcomes. This article shows distinct patterns of poverty outcomes by sector of employment, after controlling for other factors. However, household characteristics, in particular the presence of a second earner, do strongly mitigate the poverty risk. Overall, the findings demonstrate that policymakers need to develop a coherent policy towards poverty that recognises the nature of jobs growth and the distribution of ‘good jobs’ across households

Assessment of Survivor Concerns (ASC): A newly proposed brief questionnaire

BACKGROUND: The purpose of this study was to design a brief questionnaire to measure fears about recurrence and health in cancer survivors. Research involving fear of recurrence has been increasing, indicating that it is an important concern among cancer survivors. METHODS: We developed and tested a six-item instrument, the Assessment of Survivor Concerns (ASC). Construct validity was examined in a multiple group confirmatory factor analysis (CFA) with 592 short-term and 161 long-term cancer survivors. Convergent and discriminant validity was examined through comparisons with the PANAS (Positive and Negative Affect Schedule) and the CES-D (Center for Epidemiologic Studies Depression) measures. RESULTS: CFA models for the ASC with short- and long-term survivors showed good fit, with equivalent structure across both groups of cancer survivors. Convergent and discriminant validity was also supported through analyses of the PANAS and CES-D. One item (children's health worry) did not perform as well as the others, so the models were re-run with the item excluded, and the overall fit was improved. CONCLUSION: The ASC showed excellent internal consistency and validity. We recommend the revised five-item instrument as an appropriate measure for assessment of cancer survivor worries

G = MAT: Linking Transcription Factor Expression and DNA Binding Data

Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/

The purple line as a measure of labour progress: a longitudinal study

Background: Vaginal examination (VE) and assessment of the cervix is currently considered to be the gold standard for assessment of labour progress. It is however inherently imprecise with studies indicating an overall accuracy for determining the diameter of the cervix at between 48-56%. Furthermore, VEs can be unpleasant, intrusive and embarrassing for women, and are associated with the risk of introducing infection. In light of increasing concern world wide about the use of routine interventions in labour it may be time to consider alternative, less intrusive means of assessing progress in labour. The presence of a purple line during labour, seen to rise from the anal margin and extend between the buttocks as labour progresses has been reported. The study described in this paper aimed to assess in what percentage of women in labour a purple line was present, clear and measurable and to determine if any relationship existed between the length of the purple line and cervical dilatation and/or station of the fetal head. Methods: This longitudinal study observed 144 women either in spontaneous labour (n=112) or for induction of labour (n=32) from admission through to final VE. Women were examined in the lateral position and midwives recorded the presence or absence of the line throughout labour immediately before each VE. Where present, the length of the line was measured using a disposable tape measure. Within subjects correlation, chi-squared test for independence, and independent samples t-test were used to analyse the data. Results: The purple line was seen at some point in labour for 109 women (76%). There was a medium positive correlation between length of the purple line and cervical dilatation (r=+0.36, n=66, P=0.0001) and station of the fetal head (r=+0.42, n=56, P<0.0001). Conclusions: The purple line does exist and there is a medium positive correlation between its length and both cervical dilatation and station of the fetal head. Where the line is present, it may provide a useful guide for clinicians of labour progress along side other measures. Further research is required to assess whether measurement of the line is acceptable to women in labour and also clinicians