A novel experience-based internet intervention for smoking cessation : feasibility randomised controlled trial

The iPEx programme presents independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0608-10147). The views expressed in this paper are those of the authors, representing iPEx, and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewedPublisher PD

Systematic review recommends the European Organization for Research and Treatment of Cancer colorectal cancer–specific module for measuring quality of life in colorectal cancer patients

Objectives: To critically appraise the measurement properties of standardized health-related quality of life (HRQOL) instruments for colorectal cancer (CRC) patients and to provide recommendations on the choice of HRQOL instruments. Study Design and Setting: Systematic review of English language literature published between January 1985 and May 2014 identified through a database search of PubMed, Web of Science, Embase, and Ovid MEDLINE. HRQOL instruments were rated on methodological quality and overall levels of evidence using a Consensus-based Standards for the selection of health Measurement Instrument checklist. Results: Internal consistency and hypothesis testing were evaluated most frequently in 63 studies identified. The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was the most extensively evaluated. The highest number of positive ratings in the overall level of evidence was found in the CRC-specific quality of life questionnaire module (QLQ-CR38) in European Organization for Research and Treatment of Cancer (EORTC) module, followed by the Memorial Sloan Kettering Cancer Center Bowel instrument, FACT-C, and Quick-FLIC. The EORTC QLQ-CR38 had the most positive ratings on measurement property and was recommended. Conclusion: The EORTC QLQ-CR38 was recommended to assess HRQOL in patients with CRC, regardless of disease stage and primary tumor site.postprin

Genetic diversity among natural populations of Ottelia acuminata (Gaghep.) Dandy revealed by ISSR

Ottelia acuminata (Gagnep.) Dandy, an aquatic species of the Hydrocharitaceae, is endemic to China. A performance comparison of genetic diversity of 4 natural populations was conducted to investigatewhether or not water pollution in their habitats has anything to do with this species being endangered. A total number of 120 O. acuminate accessions were analyzed, by amplification of their DNAs with 15 primers (ISSR). Thirteen primers were scored and 214 bands were detected, of which 170 werepolymorphic (79.44%). The results showed that the genetic indices in polluted Jian Lake group were always the smallest ones, when compared with those of the other groups. It indicated that the polluted water did affect the genetic diversity of O. acuminate populations. And ISSRs seemed to be effectivetools for detecting genetic variation among O. acuminate geographical groups

Using Markov Models and Statistics to Learn, Extract, Fuse, and Detect Patterns in Raw Data

Many systems are partially stochastic in nature. We have derived data driven approaches for extracting stochastic state machines (Markov models) directly from observed data. This chapter provides an overview of our approach with numerous practical applications. We have used this approach for inferring shipping patterns, exploiting computer system side-channel information, and detecting botnet activities. For contrast, we include a related data-driven statistical inferencing approach that detects and localizes radiation sources.Comment: Accepted by 2017 International Symposium on Sensor Networks, Systems and Securit

The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed

Objectives To examine the reporting characteristics and methodological details of randomised trials indexed in PubMed in 2000 and 2006 and assess whether the quality of reporting has improved after publication of the Consolidated Standards of Reporting Trials (CONSORT) Statement in 2001

Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential

The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes

Heat transfer analysis in multi-layered materials with interfacial thermal resistance

Interfacial thermal resistance (ITR) presents a measure of the thermal resistance to heat transport caused by the interface in composites to a thermal movement when the heat flows across it. In the heat transfer analysis, the presence of an ITR invalidates the continuity condition of temperature at the interface, so that a special treatment is required. In this paper, two one-dimensional models are developed for the heat transfer analysis in multi-layered materials with ITR. One is to create a virtual layer at the interface to represent the ITR and the other is to use a local artificial layer surrounding the interface with modified thermal properties to reflect the influence of ITR on the heat transfer in the layer involving the interface. As the application of the present models, numerical examples are also provided for the heat transfer analysis of a multi-layered composite and a substrate with multilayer surface coatings, from which the effect of ITR on the heat transfer in composite materials is demonstrated

Assessing health research grant applications: A retrospective comparative review of a one-stage versus a two-stage application assessment process

BackgroundResearch funders use a wide variety of application assessment processes yet there is little evidence on their relative advantages and disadvantages. A broad distinction can be made between processes with a single stage assessment of full proposals and those that first invite an outline, with full proposals invited at a second stage only for those which are shortlisted. This paper examines the effects of changing from a one-stage to a two-stage process within the UK's National Institute for Health Research's (NIHR) Research for Patient Benefit (RfPB) Programme which made this change in 2015.MethodsA retrospective comparative design was used to compare eight one-stage funding competitions (912 applications) with eight two-stage funding competitions (1090 applications). Comparisons were made between the number of applications submitted, number of peer and lay reviews required, the duration of the funding round, average external peer review scores, and the total costs involved.ResultsThere was a mean number of 114 applications per funding round for the one-stage process and 136 for the two-stage process. The one-stage process took a mean of 274 days and the two-stage process 348 days to complete, although those who were not funded (i.e. the majority) were informed at a mean of 195 days (mean 79 days earlier) under the two-stage process. The mean peer review score for full applications using the one-stage process was 6.46 and for the two-stage process 6.82 (5.6% difference using a 1-10 scale (with 10 being the highest), but there was no significant difference between the lay reviewer scores. The one-stage process required a mean of 423 peer reviews and 102 lay reviewers and the two-stage process required a mean of 208 peer reviews and 50 lay reviews (mean difference of 215 peer reviews and 52 lay reviews) per funding round. Overall cost per funding round changed from £148,908 for the one-stage process to £105,342 for the two-stage process saving approximately £43,566 per round.ConclusionWe conclude that a two-stage application process increases the number of applications submitted to a funding round, is less burdensome and more efficient for all those involved with the process, is cost effective and has a small increase in peer reviewer scores. For the addition of fewer than 11 weeks to the process substantial efficiencies are gained which benefit funders, applicants and science. Funding agencies should consider adopting a two-stage application assessment process

DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that both proteins are required for normal levels of cytosine methylation and hydroxymethylation in murine embryonic stem cells. Furthermore, Mbd2 and Mbd3 regulate overlapping sets of genes that are also regulated by DNA methylation/hydroxymethylation factors. These findings reveal an interdependent regulatory mechanism mediated by the DNA methylation machinery and its readers