Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

An evaluation of commonly used external ventricular drain securement methods in a porcine model: Recommendations to improve practice

Background: External ventricular drain (EVD) dislodgement is common and leads to significant morbidity and mortality. Many securement techniques to prevent this are described. There are, however, no objective studies comparing them. This study aimed to determine the most secure method of securing an EVD. Methods: A survey was distributed through the British Neurosurgical Trainee Research Collaborative to determine common EVD securement methods and select techniques for testing. Securement methods were tested in a pig cadaver model. Peak pull force before EVD failure was measured. Failure was defined as catheter displacement 1 cm from the insertion site, catheter fracture, or suture fracture. Results: Twenty-three neurosurgical units responded. Five basic EVD securement methods were in common use. These were tested in isolation and in combination so that in total 15 common methods were tested. The most secure method was a triple construct, consisting of an anchoring suture, sutures around a coil of the catheter, and either a soft plastic flange (25.85 N, 95% confidence interval 24.95 N–26.75 N) or a hard plastic flange (29.05 N, 95% confidence interval 25.69 N–32.41 N). Of the individual methods, single anchoring sutures, soft flanges, VentriFix, and staples were found to be the least secure, whereas multiple sutures and hard flanges were the most secure. Conclusions: An anchoring suture followed by a coil of the catheter and finally a flange is the most secure method for securing EVDs. This simple technique can withstand up to 8.2 times the force of a single anchoring suture, is easily used, and decreases the likelihood of EVD dislodgement and associated complications

Participant approaches to and reflections on learning to play a 12-bar blues in an asynchronous e-learning environment

This study investigated the viability of learning to play an improvised 12-bar blues on keyboard with both hands together in an asynchronous e-learning environment. The study also sought to reveal participant approaches to and reflections on this learning experience. Parti cipants were video-taped as they engaged with six ‘Blues Activities’, supported by audio ‘guide’ and ‘backing’ tracks and a ‘remote facilitator’. Participants required nine or ten learning sessions, over a period of six weeks, to successfully complete the ‘Blues Activities’. Individual, semi-structured interviews, designed to reveal participant reflections on their engagement with the ‘Blues Activities’ were conducted with the participants after they had completed the learning sessions. Results revealed that: (1) at the end of the learning sessions, all participants were able to play the 12-bar improvised blues; (2) participants engaged in five distinct learning behaviours; and (3) four participant ‘reflective themes’ emerged from the semi-structured interviews. The five distinct learning behaviours were interpreted as ‘learning activities’: ‘instruction’, ‘copying’, ‘practising’, ‘playing’ and ‘evaluating’. The four ‘reflective themes’ were interpreted as: ‘activities’, ‘feelings’, ‘evaluation’ and ‘difficulties’. Comments made by participants during interviews and email exchanges, provided support for the researcher interpretations of the ‘learning activities’ and ‘reflective themes’ through the process of triangulation. Implications for music education are discussed