Experiences in applying skills learned in a mental health first aid training course: a qualitative study of participants' stories

BACKGROUND: Given the high prevalence of mental disorders and the comparatively low rate of professional help-seeking, it is useful for members of the public to have some skills in how to assist people developing mental disorders. A Mental Health First Aid course has been developed to provide these skills. Two randomized controlled trials of this course have shown positive effects on participants' knowledge, attitudes and behavior. However, these trials have provided limited data on participants' subsequent experiences in providing first aid. To remedy this, a study was carried out gathering stories from participants in one of the trials, 19–21 months post-training. METHODS: Former course participants were contacted and sent a questionnaire either by post or via the internet. Responses were received from 94 out of the 131 trainees who were contacted. The questionnaire asked about whether the participant had experienced a post-training situation where someone appeared to have a mental health problem and, if so, asked questions about that experience. RESULTS: Post-training experiences were reported by 78% of respondents. Five key points emerged from the qualitative data: (1) the majority of respondents had had some direct experience of a situation where mental health issues were salient and the course enabled them to take steps that led to better effects than otherwise might have been the case; (2) positive effects were experienced in terms of increased empathy and confidence, as well as being better able to handle crises; (3) the positive effects were experienced by a wide range of people with varied expectations and needs; (4) there was no evidence of people over-reaching themselves because of over-confidence and (5) those who attended were able to identify quite specific benefits and many thought the course not only very useful, but were keen to see it repeated and extended. CONCLUSION: The qualitative data confirm that most members of the public who receive Mental Health First Aid training subsequently provide support to people with mental health problems and that this support generally has positive effects

Rapid Sampling of Molecular Motions with Prior Information Constraints

Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe