The global prevalence of Wilson’s Disease from next generation sequencing data

Purpose: Wilson Disease (WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in ATP7B. We aimed to: 1) perform a meta-analysis of previous WD prevalence estimates, 2) estimate the prevalence of WD from population sequencing data, and 3) generate an ATP7B gene variant database. Methods: MEDLINE and EMBASE were systematically searched. Previous prevalence estimates were subjected to meta-analysis. All previously reported pathogenic ATP7B variants were compiled and annotated with GnomAD allele frequencies. Pooled global and ethnicity-specific genetic prevalences for WD were generated using the Hardy-Weinberg equation. Results: Meta-analysis of genetic studies of WD prevalence gave an estimate 12.7 per 100,000 (95% CI: 6.3-23.0). We developed a referenced, searchable ATP7B database comprising 11,520 variants including 782 previously reported disease variants, which can be found at http://www.wilsondisease.tk/. 216/782 of these were present in GnomAD, remained after filtering by allele frequency and met American College of Medical Genetics criteria. Based on these, the genetic prevalence of WD was 13.9 per 100,000 (95% CI: 12.9-14.9), or 1 per 7,194. Combining this with 60 predicted pathogenic variants gave a birth prevalence of 15.4 per 100,000 (95% CI: 14.4- 16.5). Conclusion: The genetic prevalence of Wilson disease may be greater than previous estimates

Evaluation of the Dads group at Blacon Children's Centre

This study was designed to evaluate Blacon Children’s Centre Dads Group. A mixed method approach was used, incorporating both quantitative and qualitative methods. Through combining the findings from the various sources, some key issues were identified, as well as areas for development. Nearly all of the dads who were attending the Dads Group, along with all of the regular service providers, participated in this study, and thus the findings should accurately reflect perceptions of the service

A generalized Pancharatnam geometric phase formula for three level systems

We describe a generalisation of the well known Pancharatnam geometric phase formula for two level systems, to evolution of a three-level system along a geodesic triangle in state space. This is achieved by using a recently developed generalisation of the Poincare sphere method, to represent pure states of a three-level quantum system in a convenient geometrical manner. The construction depends on the properties of the group SU(3)\/ and its generators in the defining representation, and uses geometrical objects and operations in an eight dimensional real Euclidean space. Implications for an n-level system are also discussed.Comment: 12 pages, Revtex, one figure, epsf used for figure insertio

Reporting and appraising the context, process and impact of PPI on contributors, researchers and the trial during a randomised controlled trial - the 3D study

Background Patient and public involvement (PPI) is believed to enhance health care delivery research, and is widely required in research proposals. Detailed, standardised reporting of PPI is needed so that strategies to implement more than token PPI that achieves impact can be identified, properly evaluated and reproduced. Impact includes effects on the research, PPI contributors and researchers. Using contributor and researcher perspectives and drawing on published guidelines for reporting PPI, we aimed to reflect on our experience and contribute evidence relevant to two important questions: ‘What difference does PPI make?’ and ‘What’s the best way to do it?’ Methods Fourteen people living with multiple long-term conditions (multimorbidity) were PPI contributors to a randomised controlled trial to improve care for people with multimorbidity. Meetings took place approximately four times a year throughout the trial, beginning at grant application stage. Meeting notes were recorded and a log of PPI involvement was kept. At the end of the trial, seven PPI contributors and four researchers completed free-text questionnaires about their experience of PPI involvement and their perception of PPI impact. The responses were analysed thematically by two PPI contributors and one researcher. The PPI group proposed writing this report, which was co-authored by three PPI contributors and two researchers. Results Meeting attendance averaged nine PPI contributors and three to four researchers. The involvement log and meeting notes recorded a wide range of activities and impact including changes to participant documentation, advice on qualitative data collection, contribution to data analysis and dissemination advice. Three themes were identified from the questionnaires: impact on the study, including keeping the research grounded in patient experience; impact on individuals, including learning from group diversity and feeling valued; and an environment that facilitated participation. The size of the group influenced impact. Researchers and PPI contributors described a rewarding interaction that benefitted them and the research. Conclusions PPI was wide-ranging and had impact on the trial, contributors and researchers. The group environment facilitated involvement. Feedback and group interactions benefitted individuals. The insights gained from this study will positively influence the researchers’ and contributors’ future involvement with PPI