A TMEFF2-regulated cell cycle derived gene signature is prognostic of recurrence risk in prostate cancer

Background: The clinical behavior of prostate cancer (PCa) is variable, and while the majority of cases remain indolent, 10% of patients progress to deadly forms of the disease. Current clinical predictors used at the time of diagnosis have limitations to accurately establish progression risk. Here we describe the development of a tumor suppressor regulated, cell-cycle gene expression based prognostic signature for PCa, and validate its independent contribution to risk stratification in several radical prostatectomy (RP) patient cohorts. Methods: We used RNA interference experiments in PCa cell lines to identify a gene expression based gene signature associated with Tmeff2, an androgen regulated, tumor suppressor gene whose expression shows remarkable heterogeneity in PCa. Gene expression was confirmed by qRT-PCR. Correlation of the signature with disease outcome (time to recurrence) was retrospectively evaluated in four geographically different cohorts of patients that underwent RP (834 samples), using multivariate logistical regression analysis. Multivariate analyses were adjusted for standard clinicopathological variables. Performance of the signature was compared to previously described gene expression based signatures using the SigCheck software. Results: Low levels of TMEFF2 mRNA significantly (p \u3c 0.0001) correlated with reduced disease-free survival (DFS) in patients from the Memorial Sloan Kettering Cancer Center (MSKCC) dataset. We identified a panel of 11 TMEFF2 regulated cell cycle related genes (TMCC11), with strong prognostic value. TMCC11 expression was significantly associated with time to recurrence after prostatectomy in four geographically different patient cohorts (2.9 ≤ HR ≥ 4.1; p ≤ 0.002), served as an independent indicator of poor prognosis in the four RP cohorts (1.96 ≤ HR ≥ 4.28; p ≤ 0.032) and improved the prognostic value of standard clinicopathological markers. The prognostic ability of TMCC11 panel exceeded previously published oncogenic gene signatures (p = 0.00017). Conclusions: This study provides evidence that the TMCC11 gene signature is a robust independent prognostic marker for PCa, reveals the value of using highly heterogeneously expressed genes, like Tmeff2, as guides to discover prognostic indicators, and suggests the possibility that low Tmeff2 expression marks a distinct subclass of PCa

The while of participation: A systematic review of participatory research involving people with sensory impairments and/or intellectual impairments.

This paper reports on the first systematic review of literature associated with participatory research involving people identified with sensory impairments and/or intel- lectual impairments. It was initiated as part of ARCHES, an European Union-funded heritage project. The review sought to examine processes and activities used for organising participatory research involving people identified with sensory and/or intellectual impairments. 54 papers were included, involving studies from 14 countries and varying numbers of participants across different time scales. Insights were gained into use of advisory groups, organisation and support, collecting and analysing data, sharing findings and activity types. Emergent themes enabled an identification of the while of participation. The while represents the tensions, outcomes and component parts which are evident within the multiple moments that span an experience of participatory research. Participation is not about types of activity but how any activity is undertaken

Exploring provision for children identified with special educational needs: an international review of policy and practice

This project aimed to create a descriptive map of international research which explores the notion of the continuum of educational provision for children with special educational needs. It also aimed to determine and examine the nature of how the continuum of provision is conceptualised, operationalised and enacted in a sample of selected countries. Commissioned by the National Council for Special Education, it also identified implications for the development of provision within the Irish context. The research involved a systematic identification and thematic review of theory, identifying and examining literature associated with the conceptualisation of the continuum; it examined the policy and provision across 55 administrations as publically reported, primarily to international agencies; it carried out more detailed examination of policy and practice in 10 countries using a survey and vignette study; and it involved a series of interviews with a range of individuals in a range of settings in four countries with differing approaches to supporting children with special educational needs. This paper outlines the overall findings of the research. It focuses in particular upon the need to change how we think about provision associated with continua, recognising the lack of international coherence in approaches to support for pupils with special educational needs. It identifies in particular the opportunities presented by a reconceptualisation of the class and the management of class resources, and the role key personnel can play in creating links between diverse services

Association of a Public Health Campaign About Coronavirus Disease 2019 Promoted by News Media and a Social Influencer With Self-reported Personal Hygiene and Physical Distancing in the Netherlands

Importance: In the absence of a vaccine and therapeutic agent, personal hygiene and physical distancing are essential measures to contain the coronavirus disease 2019 pandemic. Objective: To determine whether a social media campaign, targeted at the gaps in behavior on personal hygiene and physical distancing and distributed nationwide via digital news media, may be an effective method to improve behavior and help to inhibit person-to-person transmission of severe acute respiratory syndrome coronavirus 2. Design, Setting, and Participants: This survey study was designed to uncover self-reported gaps in behavior regarding personal hygiene and physical distancing in the Netherlands. A diagnostic survey was distributed by a large national newspaper (De Telegraaf) and a popular social influencer (Govert Sweep) on March 17, 2020, and was completed by 16 072 participants. Analysis of these outcomes showed that coughing and sneezing in the elbow was done well, but that handwashing, face touching, and physical distancing showed serious gaps compared with advised behavior. This diagnostic information was used to design infographics and a video targeted at repairing these gaps in behavior. The video and infographics were distributed on a national level on March 21, 2020, followed by a postcampaign survey to measure the results on March 24, 2020. Data analysis was performed from March to April 2020. Exposure: Exposed participants were those who viewed the infographics and/or video. Main Outcomes and Measures: Improvement on the extent of handwashing in all areas, handwashing duration of 20 seconds or longer, awareness on face touching, and physical distancing were measured according to responses on the postcampaign survey. Results: A total of 17 189 participants (mean [SD] age, 47.61 [13.57] years; 9100 women [52.9%]) responded to the postcampaign survey. The news article in De Telegraaf was read more than 2 million times, and the influencer video was watched more than 80 000 times. Cross-sectional analysis of the postcampaign survey using logistic regression correcting for age, gender, and educational level showed that exposure to the video plus infographics (827 participants) (adjusted odds ratio [OR], 2.14; 95% CI, 1.83-2.50; P < .001) and to the infographics alone (11 348 participants) (adjusted OR, 1.31; 95% CI, 1.22-1.40; P < .001) were positively associated with washing hands in all areas compared with the unexposed group (4751 participants). In addition, exposure to the video plus infographics (adjusted OR, 1.86; 95% CI, 1.59-2.16; P < .001) and to the infographics alone (adjusted OR, 1.27; 95% CI, 1.19-1.36; P < .001) were positively associated with washing hands long enough compared with the unexposed group. Exposure to the video alone was not associated with improved handwashing. Compared with the unexposed group, exposure to the infographics alone and video plus infographics were associated with improvements in physical distancing when the participant had COVID-19 syptoms (infographics alone, adjusted OR, 1.10; 95% CI, 1.03-1.17; P = .006; video plus infographics, adjusted OR, 0.79; 95% CI, 0.69-0.91; P = .001) and face touching

A cross sectional evaluation of an alcohol intervention targeting young university students

BACKGROUND: Hazardous drinking has been found to be higher among young university students compared to their non-university peers. Although young university students are exposed to new and exciting experiences, including greater availability and emphasis on social functions involving alcohol there are few multi strategy comprehensive interventions aimed at reducing alcohol-related harms. METHODS: Random cross sectional online surveys were administered to 18-24 year old students studying at the main campus of a large metropolitan university in Perth, Western Australia. Prior to the completion of the second survey an alcohol intervention was implemented on campus. Completed surveys were received from 2465 (Baseline; T1) and 2422 (Post Year 1: T2) students. Students who consumed alcohol in the past 12 months were categorised as low risk or hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT). Due to the cross sectional nature of the two samples two-tailed two-proportion z-test and two sample t-tests were employed to determine statistical significance between the two time periods for categorical and continuous variables respectively. RESULTS: At T1 and T2 89.1 % and 87.2 % of the total sample reported drinking alcohol in the past month respectively. Hazardous levels of alcohol consumption reduced slightly between T1 (39.7 %) and T2 (38 %). In both time periods hazardous drinkers reported significantly higher mean scores for experienced harm, second-hand harm and witnessed harm scores compared to low risk drinkers (p &lt;0.001). Hazardous drinkers were significantly more likely to experience academic problems due to their alcohol consumption and to report more positive alcohol expectations than low risk drinkers at both time periods (p &lt;0.001). CONCLUSIONS: Harms and problems for students who report hazardous drinking are of concern and efforts should be made to ensure integrated and targeted strategies reach higher risk students and focus on specific issues such as driving while intoxicated and alcohol related unplanned sexual activity. However there is also a need for universal strategies targeting all students and low risk drinkers as they too are exposed to alcohol harms within the drinking and social environment. Changing the culture of the university environment is a long term aim and to effect change a sustained combination of organisational actions, partnerships and educational actions is required

"What Do They Want Me To Say?" The hidden curriculum at work in the medical school selection process: a qualitative study

<p>Abstract</p> <p>Background</p> <p>There has been little study of the role of the essay question in selection for medical school. The purpose of this study was to obtain a better understanding of how applicants approached the essay questions used in selection at our medical school in 2007.</p> <p>Methods</p> <p>The authors conducted a qualitative analysis of 210 essays written as part of the medical school admissions process, and developed a conceptual framework to describe the relationships, ideas and concepts observed in the data.</p> <p>Results</p> <p>Findings of this analysis were confirmed in interviews with applicants and assessors. Analysis revealed a tension between "genuine" and "expected" responses that we believe applicants experience when choosing how to answer questions in the admissions process. A theory named "What do they want me to say?" was developed to describe the ways in which applicants modulate their responses to conform to their expectations of the selection process; the elements of this theory were confirmed in interviews with applicants and assessors.</p> <p>Conclusions</p> <p>This work suggests the existence of a "hidden curriculum of admissions" and demonstrates that the process of selection has a strong influence on applicant response. This paper suggests ways that selection might be modified to address this effect. Studies such as this can help us to appreciate the unintended consequences of admissions processes and can identify ways to make the selection process more consistent, transparent and fair.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin