Shifting Demand for Non Medical Services Evaluation Report

This evaluation looked at the feasibility and utility of a city-wide, brief intervention provided by community support workers to link people with non-medical issues to a range of services and support. The GP referral system effectively identified people at high risk of avoidable hospital admissions. Over 90% of patients referred received an assessment from a community support worker (CSW). The approach used by CSWs was consistent with the international evidence base for providing effective peer support. Clients initially self-reported reduced anxiety and social isolation. After being linked, however, there were delays in getting needs met, leading to disengagement and return to the high risk group. Effectiveness of the service is dependent upon the capacity and responsiveness of the sectors to which clients are referred.<br

Identification of New Differentially Methylated Genes That Have Potential Functional Consequences in Prostate Cancer

<div><p>Many differentially methylated genes have been identified in prostate cancer (PCa), primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (<em>n</em> = 19) and adjacent normal tissues (<em>n</em> = 4) and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted <em>P</em><0.05), defined as a mean methylation difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa). Aberrant DNA methylation of two genes, <em>AOX1</em> and <em>SPON2,</em> were confirmed via bisulfate sequencing, with most of the respective CpG sites showing significant differences between tumor samples and normal tissues. The <em>AOX1</em> promoter region showed hypermethylation in 92.6% of 54 tested PCa samples in contrast to only three out of 53 tested normal tissues. This study used a new BeadChip combined with gene expression data in PCa to identify novel differentially methylated CpG sites located within genes. The newly identified differentially methylated genes may be used as biomarkers for PCa diagnosis.</p> </div

Differential <i>SPON2</i> promoter methylation in PCa samples and normal prostate tissues.

<p>Each circle or square represents the average methylation of 27 tested CpG sites in each phenotype. Error bars indicate 95% confidence intervals for each CpG site.</p

Differential <i>AOX1</i> promoter methylation in PCa samples and normal prostate tissues.

<p>A. Average methylation of 34 tested CpG sites in each phenotype. Error bars indicate 95% confidence intervals for each CpG site. B. Distribution of <i>AOX1</i> promoter methylation in each phenotype. Each circle or square represents the average methylation of 34 tested CpG sites in each tested tissue sample.</p

Distribution of differentially methylated CpG sites in genomic regions.

*<p>CGI: CGIs, CGI shores, and CGI shelves.</p>*<p>promoter: TSS1500, TSS200, 5′UTR, and 1st exon.</p>*<p>non-promoter: gene body and 3′UTR.</p

Hypermethylated (top 10) and hypomethylated (all) genes in PCa^*.

†<p>Expression <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048455#pone.0048455-Taylor1" target="_blank">[29]</a>, HM27 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048455#pone.0048455-Kobayashi1" target="_blank">[18]</a>, M-NGS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048455#pone.0048455-Kim1" target="_blank">[16]</a>, Known methylated gene <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048455#pone.0048455-Ongenaert1" target="_blank">[10]</a>.</p>‡<p>Difference between PCa and normal (Tumor - Normal). Δβ (methylation difference) indicated the biggest difference among multiple DMCs.</p>#<p>Only located in the proximal promoter.</p>*<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048455#pone.0048455.s012" target="_blank">Table S5</a> for the full list of 122 genes.</p

Schematic of selection procedure to identify differentially methylated CpG sites.

<p>Schematic of selection procedure to identify differentially methylated CpG sites.</p

Additional file 4 of A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND): study protocol

Additional file 4. Example consent form