How NICE may be outflanked.
Ontology highlight
ABSTRACT:
SUBMITTER: Ferner RE
PROVIDER: S-EPMC1471969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mammalian chromatin is dynamic and contains structural information that leads to transcriptional regulation of genes by recruiting transcription factors and altering nucleosome positioning. Here, we describe open chromatin mapping using Nicking Enzyme assisted sequencing (NicE-seq) for integrative epigenomic analysis. NicE-seq captures open chromatin sites in both fixed and native cells and reveals the genomic location of open chromatin sites (OCS) and transcription factor occupancy at single nucleotide resolution, with as few as 250 HCT116 cells. In HCT116 cells a large percentage of the OCS were coincident with DHS (DNaseI hypersensitive site) and ATAC-seq sites. OCSs correlated well with RNA pol II occupancy and transcriptionally active chromatin marks, while displaying a pattern contrasting to CpG methylation. ChIP CTCF peaks common to OCS and DHS displayed a strong correlation with H3K4me3 and H3K27ac marks. Further peaks unique to OCS and ChIP CTCF peaks also correlated strongly with H3K4me3, H3K27ac and higher transcription. Similar results were also obtained for Max and Sp1 transcription factors. Using NicE-seq we have demonstrated that HCT116 cells, treated with anti cancer drug decitabine, displayed time dependent accumulation of OCS coinciding with hypomethylation of the genome, particularly in SINE and satellite repetitive DNA. Differentially methylated regions (DMRs) were more pronounced in promoters, 5’UTR, CpG islands and exons. In summary, sequence specificity offered by a nicking enzyme allows a means to study open chromatin structure and hypomethylation of genomes, revealing the open chromatin landscape in cellular context.
2017-05-24 | GSE97889 | GEO
Project description:National Institute for Health and Clinical Excellence (NICE) clinical guidelines and subsequent NICE issued 'recommendation reminders' advocate discontinuing two fertility procedures and caesarean sections in women with hepatitis. We assess whether NICE guidance in 2004 and recommendation reminders were associated with a change in the rate of clinical procedures performed.Routine inpatient Hospital Episode Statistics (HES) data were extracted from the HES database for 1st April 1998 to 31st March 2010 using OPCS procedure codes for varicocele operations in infertile men, endometrial biopsies in infertile women and caesarean sections in women with hepatitis B or C. We used Joinpoint regression to identify points in time when the trend in procedure rates changed markedly, to identify any influence of the release of NICE guidance.Between 1998-2010, planned caesarean sections in women with and without hepatitis B or C increased yearly (annual percentage change (APC) 4.9%, 95% CI 2.1% to 7.7%) in women with hepatitis, compared with women without (APC 4.0% [95% CI 2.7% to 5.3%] up to 2001, APC -0.6% [95% CI -2.8% to 1.8%] up to 2004 and 1.3% [95% CI 0.8% to 1.8%] up to 2010). In infertile women under 40 years of age, endometrial biopsies for investigation of infertility increased, APC 6.0% (95% CI 3.6% to 8.4%) up to 2003, APC 1.5% (95% CI -4.3% to 7.7%) to 2007 followed by APC 12.8% (95% CI 1.0% to 26.0%) to 2010. Varicocele procedures remained relatively static between 1998 and 2010 (APC -0.5%, 95% CI -2.3% to 1.3%).There was no decline in use of the three studied procedures, contrary to NICE guidance, and no change in uptake associated with the timing of NICE guidance or recommendation reminders. 'Do not do' recommendation reminders may be ineffective at improving clinical practice or achieving disinvestment.
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Project description:Open chromatin profiling integrates information across diverse regulatory elements to reveal the transcriptionally active genome. Tn5 transposase and DNase I sequencing-based methods prefer native or high cell numbers. Here, we describe NicE-seq (nicking enzyme assisted sequencing) for high-resolution open chromatin profiling on both native and formaldehyde-fixed cells. NicE-seq captures and reveals open chromatin sites (OCSs) and transcription factor occupancy at single nucleotide resolution, coincident with DNase hypersensitive and ATAC-seq sites at a low sequencing burden. OCSs correlate with RNA polymerase II occupancy and active chromatin marks, while displaying a contrasting pattern to CpG methylation. Decitabine-mediated hypomethylation of HCT116 displays higher numbers of OCSs.
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Project description:The syntactic organization of incidentally presented word pairs may affect behavior by providing actors with implicit propositions about how to behave. In Experiment 1, participants who had already played turns of a mixed-motive game were less cooperative after an explicit propositional suggestion that they had been nice in prior turns but were more cooperative after the suggestion that they should be nice in upcoming turns. In three subsequent experiments, implicit priming with the phrase nice act produced greater levels of defection, implying that actors responded to the implicit suggestion that they had been sufficiently nice already. In contrast, act nice produced greater levels of cooperation, implying that actors responded to the implicit suggestion that they should try to be nicer in upcoming turns. These effects occurred outside of awareness and disappeared when the interval between the words was long and when behavior was measured after a delay.
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Project description:Determination of accessible chromatin regions in the 8-cell stage mouse embryo after Suv39h2 knockdown The study aimed to address a potential function of H3K9me3 in early mouse development by assessing its impact on chromatin compaction. The histone methyltransferase responsible for de novo H3K9me3 at fertilization Suv39h2, was knocked down by microinjection of dsRNA targeting Suv39h2 in the early zygote. Embryos were then cultured until the 8-cell stage of development. They were then fixed and chromatin compaction was assessed by NicE-seq in pools of 10 8-cell stage embryos.
2020-03-31 | GSE138686 | GEO
Project description:BackgroundThere is growing interest internationally in linking reimbursement decisions with recommendations for further research. In the UK, the National Institute for Health and Clinical Excellence (NICE) can issue guidance to approve the routine use of a health intervention, reject routine use or recommend use within a research programme. These latter recommendations have restricted use to 'only in research' (OIR) or have recommended further research alongside routine use ('approval with research' or AWR). However, it is not currently clear when such recommendations are likely to be made.ObjectivesThis study aims to identify NICE technology appraisals where OIR or AWR recommendations were made and to examine the key considerations that led to those decisions.MethodsDraft and final guidance including OIR/AWR recommendations were identified. The documents were reviewed to establish the characteristics of the technology appraisal, the cost effectiveness of the technologies, the key considerations that led to the recommendations and the types of research required.ResultsIn total, 29 final and 31 draft guidance documents included OIR/AWR recommendations up to January 2010. Overall, 86 % of final guidance included OIR recommendations. Of these, the majority were for technologies considered to be cost ineffective (83 %) and the majority of final guidance (66 %) specified the need for further evidence on relative effectiveness. The use of OIR/AWR recommendations is decreasing over time and they have rarely been used in appraisals conducted through the single technology appraisal process.ConclusionNICE has used its ability to recommend technologies within research programmes, although predominantly within the multiple technology appraisal process. OIR recommendations have been most frequently issued for technologies considered cost ineffective and the most frequently cited consideration is uncertainty related to relative effectiveness. Key considerations cited for most AWR recommendations and some OIR recommendations included a need for further evidence on long-term outcomes and adverse effects of treatment.
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